PKU (Phenylketonuria) in your baby

Phenylketonuria (also called PKU) is a condition in which your body can’t break down an amino acid called phenylalanine. Amino acids help build protein in your body. Without treatment, phenylalanine builds up in the blood and causes health problems.

In the United States, about 1 in 10,000 to 15,000 babies is born with PKU each year. The illness happens in all ethnic groups. But it’s more common in people who are Native American and Northern European than those who are African-American, Ashkenazi Jewish or Japanese.

What causes PKU?
PKU is inherited. This means it’s passed from parent to child through genes. A gene is a part of your body’s cells that stores instructions for the way your body grows and works. Genes come in pairs—you get one of each pair from each parent.

Sometimes the instructions in genes change. This is called a gene change or a mutation. Parents can pass gene changes to their children. Sometimes a gene change can cause a gene to not work correctly. Sometimes it can cause birth defects or other health conditions. A birth defect is a health condition that is present in a baby at birth.

Your baby has to inherit a gene change for PKU from both parents to have PKU. If she inherits the gene from just one parent, she has the gene change for PKU, but she doesn’t have PKU. When this happens, your baby is called a PKU carrier. A PKU carrier has the gene change but doesn’t have PKU.

How do you know if your baby has PKU?
All babies have a newborn screening test for PKU. Newborn screening checks for serious but rare conditions at birth. It includes blood, hearing and heart screening. With newborn screening, PKU can be found and treated early so babies can grow up healthy.

Before your baby leaves the hospital, his health care provider takes a few drops of blood from his heel. The blood is collected on a special paper and sent to a lab for testing. The lab then sends the results back to your baby’s provider.

If newborn screening results aren’t normal, it simply means your baby needs more testing. Your baby’s provider can recommend another kind of test, called a diagnostic test. This test can check to see if your baby has PKU or if there is some other cause for abnormal test results.

If your baby is tested before he’s a full day old, it’s possible for the test to miss PKU. Some experts recommend that if your baby was tested within the first 24 hours of life, he should be tested again at 1 to 2 weeks of age.

What problems can PKU cause?
Babies born with PKU seem normal for the first few months of life. But without treatment, they begin to have signs and symptoms of the illness at about 6 months of age. These include:

  • Jerky movements in arms and legs
  • Lighter skin and eyes (Babies with PKU can’t properly make melanin, the pigment in the body that’s responsible for skin and hair color.)
  • Musty body smell
  • Seizures
  • Skin rashes
  • Small head size
  • Taking longer than expected to sit, crawl or walk
  • Losing interest in surroundings
  • Delays in mental and social skills
  • Intellectual disabilities
  • Behavior problems, like being hyperactive

If your baby has PKU, what kind of treatment does he need?
If your baby has PKU, he may need testing as often as once a week or more often for the first year of life to check his phenylalanine levels. After that, he may have testing once or twice a month throughout childhood.

Your baby needs to follow a special meal plan that is low in phenylalanine. It’s best to start this meal plan as soon as possible, ideally within the first 7 to 10 days of life.

At first, your baby gets a special protein formula that has reduced phenylalanine. Protein is important to help your baby grow and develop. The amount of phylalanine in the formula is controlled to meet you baby’s individual needs. Your baby also can have some breast milk. Your breast milk has phenylalanine in it, so talk to your baby’s provider to find out how much breast milk your baby can have.

When your baby is ready to eat solid foods, she can eat vegetables, fruits, some grains (like low-protein cereals, breads and pasta) and other low-phenylalanine foods. If your baby has PKU, she should not eat:

  • Milk, cheese, ice cream and other dairy products
  • Eggs
  • Meat and poultry
  • Fish
  • Nuts
  • Beans
  • Food or drinks that contain aspartame. This is an artificial sweetener that has lots of phenylalanine in it. It’s sold as NutraSweet® and Equal®.

PKU meal plans are different for each baby and can vary over time depending on how much phenylalanine your baby can take. Health care providers at a medical center or clinic that has a special program to treat PKU can help you create a PKU meal plan for your baby. Ask your baby’s health care provider for information on a medical center or clinic that treats PKU.

Your child follows the PKU meal plan through her whole life. If she eventually gets pregnant, she follows her meal plan throughout pregnancy. Most pregnant women who have PKU can have healthy pregnancies and healthy babies.

The medicine Kuvan® (sapropterin dihydrochloride) can help some people with PKU. The medicine is more likely to work in people with mild or special forms of PKU. Children who take Kuvan® must follow a special meal plan, but it may not be as strict as one for those not taking the drug. They still need regular blood tests to check phenylalanine levels.

For more information
National PKU News
Serum phenylalanine screening
Genetics Home Reference: PKU
MedlinePlus: PKU

Last reviewed February 2013

See also: Genetic counseling, Newborn screening

Most common questions

Can dad's exposure to chemicals harm his future kids?

Dad's exposure to harmful chemicals and substances before conception or during his partner's pregnancy can affect his children. Harmful exposures can include drugs (prescription, over-the-counter and illegal drugs), alcohol, cigarettes, cigarette smoke, chemotherapy and radiation. They also include exposure to lead, mercury and pesticides.

Unlike mom's exposures, dad's exposures do not appear to cause birth defects. They can, however, damage a man's sperm quality, causing fertility problems and miscarriage. Some exposures may cause genetic changes in sperm that may increase the risk of childhood cancer. Cancer treatments, like chemotherapy and radiation, can seriously alter sperm, at least for a few months post treatment. Some men choose to bank their sperm to preserve its integrity before they receive treatment. If you have a question about a specific exposure, contact the Organization of Teratology Information Specialists at www.otispregnancy.org.

Can Rh factor affect my baby?

The Rh factor may be a problem if mom is Rh-negative but dad is Rh-positive. If dad is Rh-negative, there is no risk.

If your baby gets her Rh-positive factor from dad, your body may believe that your baby's red blood cells are foreign elements attacking you. Your body may make antibodies to fight them. This is called sensitization.

If you're Rh-negative, you can get shots of Rh immune globulin (RhIg) to stop your body from attacking your baby. It's best to get these shots at 28 weeks of pregnancy and again within 72 hours of giving birth if a blood test shows that your baby is Rh-positive. You won't need anymore shots after giving birth if your baby is Rh-negative. You should also get a shot after certain pregnancy exams like an amniocentesis, a chorionic villus sampling or an external cephalic version (when your provider tries to turn a breech-position baby head down before labor). You'll also want to get the shot if you have a miscarriage, an ectopic pregnancy or suffer abdominal trauma.

Does cleft lip or cleft palate cause dental problems?

A cleft lip or cleft palate that extends into the upper gums (where top teeth develop) can cause your baby to have certain dental problems, including:

  • Missing teeth
  • Too many teeth
  • Oddly shaped teeth
  • Teeth that are out of position around the cleft

Every baby with a cleft lip or palate should get regular dental checkups by a dentist with experience taking care of children with oral clefts. Dental problems caused by cleft lip or palate usually can be fixed. If needed, your baby can get ongoing care by a team of experts, including:

  • A dentist
  • An orthodontist to move teeth using braces
  • An oral surgeon to reposition parts of the upper jaw, if needed, and to fix the cleft

See also:

 

Does cleft lip or cleft palate cause ear problems?

Cleft lip does not cause ear problems.

Babies with cleft palate, however, are more likely than other babies to have ear infections and, in some cases, hearing loss. This is because cleft palate can cause fluid to build up in your baby’s middle ear. The fluid can become infected and cause fever and earache. If fluid keeps building up with or without infection, it can cause mild to moderate hearing loss.

Without treatment , hearing loss can affect your baby’s language development and may become permanent.

With the right care, this kind of hearing loss is usually temporary. Your baby’s provider may recommend:

  • Having your baby’s ears checked regularly for fluid buildup
  • Medicines for treating fluid buildup and ear infections
  • Ear tubes if your baby has fluid in his ears over and over again. Ear tubes are tiny tubes that are inserted into the eardrum to drain the fluid and help prevent infections.

See also:

Does cleft lip or cleft palate cause problems with breastfeeding?

Babies with only a cleft lip usually don’t have trouble breastfeeding. Most of the time, they can breastfeed just fine. But they may need some extra time to get started.

Babies with cleft lip and palate or with isolated cleft palate can have:

  • Trouble sucking strong enough to draw milk through a nipple
  • Problems with gagging or choking
  • Problems with milk coming through the nose while feeding

Most babies with cleft palate can’t feed from the breast. If your baby has cleft palate, he can still get the health benefits of breastfeeding if you feed him breast milk from a bottle. Your provider can show you how to express (pump) milk from your breasts and store breast milk.

Your baby’s provider can help you start good breastfeeding habits right after your baby is born. She may recommend:

  • Special nipples and bottles that can make feeding breast milk from a bottle easier
  • An obturator. This is a small plastic plate that fits into the roof of your baby’s mouth and covers the cleft opening during feeding.

See also: , Breastfeeding

Does cleft lip or cleft palate cause speech problems?

Children with cleft lip generally have normal speech. Children with cleft lip and palate or isolated cleft palate may:

  • Develop speech more slowly
  • Have a nasal sound when speaking
  • Have trouble making certain sounds

Most children can develop normal speech after having cleft palate repair. However, some children may need speech therapy to help develop normal speech.

See also:

What are choroid plexus cysts?

The choroid plexus is the area of the brain that produces the fluid that surrounds the brain and spinal cord. This is not an area of the brain that involves learning or thinking. Occasionally, one or more cysts can form in the choroid plexus. These cysts are made of blood vessels and tissue. They do not cause intellectual disabilities or learning problems. Using ultrasound, a health care provider can see these cysts in about 1 in 120 pregnancies at 15 to 20 weeks gestation. Most disappear during pregnancy or within several months after birth and are no risk to the baby. They aren't a problem by themselves. But if screening tests show other signs of risk, they may indicate a possible genetic defect. In this case, testing with higher-level ultrasound and/or amniocentesis may be recommended to confirm or rule out serious problems.

What if I didn't take folic acid before pregnancy?

If you didn’t take folic acid before getting pregnant, it doesn't necessarily mean that your baby will be born with birth defects. If women of childbearing age take 400 micrograms of folic acid every day before and during early pregnancy, it may help reduce their baby’s risk for birth defects of the brain and spin called . But it only works if you take it before getting pregnant and during the first few weeks of pregnancy, often before you may even know you’re pregnant.

Because nearly half of all pregnancies in the United States are unplanned, it's important that all women of childbearing age (even if they're not trying to get pregnant) get at least 400 micrograms of folic acid every day. Take a multivitamin with folic acid before pregnancy. During pregnancy, switch to a prenatal vitamin, which should have 600 micrograms of folic acid.

Last reviewed November 2012

Achondroplasia

Achondroplasia is a genetic disorder of bone growth that is evident at birth. It affects about 1 in 15,000 to 1 in 40,000 births, and it occurs in all races and in both sexes (1). Its depiction in ancient Egyptian art makes it one of the oldest recorded birth defects.

Achondroplasia is the most common of a group of growth defects characterized by abnormal body proportions. Affected individuals have arms and legs that are very short, while the torso is nearly normal size.

The word achondroplasia is Greek and means "without cartilage formation," although individuals with achondroplasia do have cartilage. During fetal development and childhood, cartilage normally develops into bone, except in a few places, such as the nose and ears. In individuals with achondroplasia, something goes wrong during this process, especially in the long bones (such as those of the upper arms and thighs). The rate at which cartilage cells in the growth plates of the long bones turn into bone is slow, leading to short bones and reduced height.

What does a person with achondroplasia look like?

A child with achondroplasia has a relatively normal torso and short arms and legs. The upper arms and thighs are more shortened than the forearms and lower legs. Generally, the head is large, the forehead is prominent and the nose is flat at the bridge. Sometimes, the large head size reflects hydrocephalus (excess fluid in the brain) and requires surgery. Hands are short with stubby fingers. There is a separation between the middle and ring fingers (trident hand). Feet are generally short, broad and flat. Most individuals with achondroplasia eventually reach an adult height of about 4 feet (1, 2).

How is achondroplasia diagnosed?

At birth or during infancy, achondroplasia is generally diagnosed with x-rays and a physical examination. If there is any question about the diagnosis, genetic testing using a blood sample can be done to look for a mutation (change) in the gene that causes achondroplasia.

Before birth, achondroplasia may be suspected in the fetus if an ultrasound shows shortened bones and other bone abnormalities. In such cases, the health care provider may recommend amniocentesis to confirm the diagnosis.

How does achondroplasia affect development?

Individuals with achondroplasia usually have normal intelligence and a normal life span (1). However, affected children have a number of medical complications that can affect their development.

Babies with achondroplasia have poor muscle tone, often leading to delays in learning to sit, stand and walk. Before beginning to walk, a baby with achondroplasia often develops a small hump (kyphosis) on his upper back. This is due to poor muscle tone and usually goes away after the child starts walking. Babies with achondroplasia should not be placed in umbrella-type strollers or other carriers that do not provide good back support, because lack of support can contribute to development of a hump in the back. Once walking, the child usually develops a markedly curved lower spine (lordosis or sway-back), and the lower legs often become bowed.

Children with achondroplasia have narrow passages in the nose that can contribute to ear infections and, without treatment, to hearing loss. Due to a small jaw, teeth may be crowded, and upper and lower teeth may be poorly aligned.

Occasionally, a baby or young child with achondroplasia may die suddenly, often during sleep. This occurs in 2 to 5 percent of affected babies (2). These deaths can result from compression of the upper end of the spinal cord, which can interfere with breathing. The compression is caused by abnormalities in the size and structure of the opening in the base of the skull (foramen magnum) and vertebrae in the neck through which the spinal cord descends. All babies and young children with achondroplasia should be evaluated for foramen magnum compression.

Adolescents and adults with achondroplasia often develop low back pain or weakness, tingling and pain in the legs. This often is due to pressure on the spinal cord from a small spinal canal (called spinal stenosis).

How is achondroplasia treated?

Health care providers closely monitor the growth and development of children with achondroplasia. Though there is currently no way to normalize skeletal development of children with the disorder, most complications can be effectively treated.

Infants and children with achondroplasia should be thoroughly evaluated for skeletal abnormalities by a doctor experienced with the disorder. The doctor follows the child’s development using special charts of head and body growth for children with achondroplasia. If the head is becoming too large, the doctor tests the child for hydrocephalus. If necessary, a neurosurgeon inserts a shunt to drain the excess fluid and relieve pressure on the brain.

The child also is monitored for signs of upper spinal cord compression (due to foramen magnum abnormalities), using imaging tests such as computed tomography (CT scan or CAT scan) or magnetic resonance imaging (MRI). Possible symptoms of spinal cord compression may include snoring, sleep apnea (episodes where the baby stops breathing while sleeping) and persistent low muscle tone. When necessary, surgery can widen the opening and relieve pressure on the spinal cord.

Some children also may have breathing problems caused by small facial structures, large tonsils or a small chest size. Surgery to remove the tonsils and adenoids (lymph tissue near the throat) often improves these breathing problems.

If kyphosis (small hump) does not go away after a child begins walking, a back brace may be used to correct it. Surgery can correct bowing of the legs, especially if the bowing becomes severe or causes pain.

Children with achondroplasia often require placement of middle-ear drainage tubes. This helps to prevent hearing loss that can occur with frequent ear infections. Dental problems caused by overcrowding of teeth may require extra routine care and braces.

Children with achondroplasia tend to put on extra weight, starting at an early age. Because excessive weight can further aggravate skeletal problems, affected children should receive nutritional guidance to help prevent obesity.

Physical activity can help control weight. The American Academy of Pediatrics (AAP) recommends activities, such as swimming and biking (2). Children with achondroplasia should avoid gymnastics and collision sports because of the risk of spinal complications (2).

Some medical centers are evaluating the use of human growth hormone to improve the growth of children with achondroplasia. To date, some children have achieved modest increases in growth after 1 to 2 years of treatment (1, 2). However, no study has demonstrated that this treatment significantly increases eventual adult height (1, 2).

Leg-lengthening surgeries can increase the height of someone with achondroplasia by up to 12 to 14 inches (1, 3). This procedure is controversial because it requires a long duration of treatment (up to 2 years) and is associated with many complications. Little People of America (LPA), an advocacy organization for individuals of short stature and their families, recommends postponing any decisions about this surgery until the young person is able to fully participate in decision making (4).

What is the cause of achondroplasia?

Achondroplasia is caused by a mutation in a gene (called fibroblast growth factor receptor 3) that is located on chromosome 4 (5, 6). This gene normally helps regulate the rate of growth in long bones. Mutations in this gene result in severely limited bone growth.

In a small number of cases, a child inherits achondroplasia from a parent who also has the condition. If one parent has the condition and the other does not, there is a 50 percent chance that their child will be affected. If both parents have achondroplasia, there is:

  • A 50 percent chance that the child will inherit the condition
  • A 25 percent chance that the child will not have it
  • A 25 percent chance that the child will inherit one abnormal gene from each parent and have severe skeletal abnormalities that lead to early death

When both parents have achondroplasia, providers generally offer them prenatal tests to diagnose or rule out the fatal form of the disease. A child who does not inherit the condition cannot pass it on to his or her own children.

In more than 80 percent of cases, however, achondroplasia is not inherited but results from a new mutation that occurs in the egg or sperm cell that forms the embryo (1, 3). Parents of children with achondroplasia resulting from a new mutation usually are normal sized. Typically, these parents have no other children with achondroplasia, and the chances of their having a second affected child are extremely small.

Geneticists have observed that older-than-average fathers (40 and older) are more likely to have children with achondroplasia and certain other autosomal-dominant conditions (disorders that occur when one gene in a gene pair is abnormal) caused by new mutations (1, 3). Individuals with achondroplasia resulting from new mutations transmit the disorder to their children as previously described.

Can achondroplasia be prevented?

There is no way to prevent most cases of achondroplasia because they result from totally unexpected gene mutations in unaffected parents. Genetic counseling can help adults with achondroplasia and unaffected individuals who have had an affected child make informed decisions about family planning.

Does the March of Dimes support research on achondroplasia and other forms of disproportionate short stature?
March of Dimes grantees are studying how abnormalities in the structure or function of the fibroblast growth factor receptor 3 gene may cause the features of achondroplasia. For example, one grantee is studying interactions between this gene and a cell-to-cell signaling pathway that plays a role in bone development. The goal of this research is to develop treatments for achondroplasia and other skeletal disorders caused by this gene. Other recent grantees have been working to identify the genes that cause some of the other more than 100 forms of disproportionate short stature (1).

For more information on achondroplasia and other forms of growth deficiency

Little People of America (LPA)
Human Growth Foundation
The Magic Foundation for Children’s Growth and Related Adult Disorders

References

  1. Francomano, C.A. Achondroplasia. GeneReviews, University of Washington, Seattle. Updated 1/9/06, accessed 7/23/08, www.genetests.org.
  2. Trotter, T.L, Hall, J.G., and the American Academy of Pediatrics Committee on Genetics. Health Supervision for Children with Achondroplasia. Pediatrics, volume 116, number 3, September 2005, pages 771-783.
  3. Horton, W.A., et al. Achondroplasia. The Lancet, volume 370, July 14, 2007, pages 162-172.
  4. Little People of America (LPA). Extended Limb Lengthening: Little People of America Medical Advisory Board Position Summary, 2006.
  5. Rousseau, F., et al. Mutations in the Gene Encoding Fibroblast Growth Factor Receptor 3 in Achondroplasia. Nature, volume 371, September 15, 1994, pages 252-254.
  6. Shiang, R., et al. Mutations in the Transmembrane Domain of FGFR3 Cause the Most Common Genetic Form of Dwarfism, Achondroplasia. Cell, volume 78, July 29, 1994, pages 335-342.

September 2008

Autism

Autism spectrum disorders (ASDs) is a group of conditions that affect how a child functions in several areas, including speech, social skills and behavior. Symptoms of these disorders vary greatly and range from mild to severe.

There are three main types of ASDs (1):

  • Autistic disorder (also called classic autism): Affected individuals often have severe speech, social and behavioral problems. Sometimes individuals also have intellectual disability.
  • Asperger syndrome: Affected individuals have milder social and behavioral problems than individuals with autistic disorder. They usually have normal speech and intellectual abilities.
  • Pervasive developmental disorder not otherwise specified (also called atypical autism): Affected individuals have some symptoms, often including speech and social problems, but not enough to be diagnosed with classic autism.

The American Academy of Pediatrics (AAP) recommends that all children be screened for ASDs at their regular medical checkups at 18 months and 24 months (2). Early diagnosis and treatment can greatly improve the outlook for children with ASDs.

How common are ASDs?
ASDs may affect about 1 in 110 to 1 in 150 children in the United States (3, 4). This means there may be more than 650,000 children in this country who have some symptoms of autism (4).

More children than ever are being diagnosed with ASDs. The rates of children diagnosed with ASDs have risen dramatically since the 1980s; between 2002 and 2006 they increased 57 percent, from 6.0 to 9.4 cases per 1,000 (3). Much of this increase may be due to improved awareness and changes in how ASDs are diagnosed.

What are the symptoms of ASDs?
Each child with an ASD is unique. Common characteristics and behaviors include a child who (1, 5):

  • Does not speak (about 40 percent of children with autistic disorder do not speak at all)
  • Repeats words
  • Performs repetitive movements, such as hand-flapping
  • Doesn’t play “pretend” games
  • Is overly active
  • Has frequent temper tantrums
  • Avoids eye contact
  • Has difficulty starting and maintaining conversation and making friends
  • Does not respond to being called by name
  • Insists on keeping the same routine
  • Repeats actions again and again
  • Focuses on a single subject or activity
  • Wants to be alone
  • Is overly sensitive to the way things feel, sound, taste or smell
  • Dislikes being held or cuddled
  • Has sleep disturbances
  • Lacks fear in risky situations
  • Has some degree of intellectual disability or learning problems
  • Is aggressive
  • Hurts himself
  • Loses skills (for example, stops saying words he used to say)

When is an ASD diagnosed?
A child with an ASD usually does not look different from other children. He may appear to develop normally for the first year or so of life. But during the second year, some children with an ASD begin to fall behind in social skills, fail to develop speech, or even lose skills that they had previously acquired. An ASD is often diagnosed around age 3; however, subtle signs of the disorder may appear before 18 months (2). These signs may include (2):

  • Not turning when the parent says the baby’s name
  • A lack of back-and-forth babbling with parents starting around 6 months of age
  • Late smiling
  • Not looking when a parent points and says, “Look at…”

Toddlers with these signs do not necessarily have an ASD, as each child develops at a different rate. However, parents should discuss these possible signs and other developmental concerns with their baby’s health care provider.

Speech delays can be early signs of ASDs. AAP recommends an immediate evaluation for ASDs if the child (2):

  • Does not babble, point or use other gestures by 12 months
  • Does not say any single words by 16 months
  • Does not say any 2-word phrases by 24 months
  • Loses language or social skills at any age

How are ASDs diagnosed?
There is no specific medical test to diagnose ASDs. Health care providers generally diagnose ASDs by observing a child’s behavior. They also use screening tests that measure a number of characteristics and behaviors associated with ASDs. If a screening test suggests a possible problem, the provider may do additional tests or recommend evaluation by a specialist.

Who is at risk of an ASD?
ASDs occur in all racial, social and educational groups. Boys are about 4 times more likely than girls to be affected (1). Siblings of an affected child may be at increased risk of ASDs, though the risk appears fairly low at 2 to 8 percent (1, 2).

Recent studies suggest that premature babies may be at increased risk of symptoms associated with ASDs (6, 7). A premature baby is a baby born before 37 completed weeks of pregnancy. Some of the increased risk is because of the higher rates of problems associated with premature birth (7, 8, 9). These problems include:

  • Pregnancy complications, such as preeclampsia, a pregnancy-related form of high blood pressure
  • Newborn health problems, such as brain bleeds
  • Lasting disabilities, such as cerebral palsy, intellectual disabilities, and vision and hearing impairments

What causes ASDs?
We don’t really understand the causes of ASDs. But scientists do know that autism is not caused by poor parenting or other social factors. It is a biological disorder that appears to be associated with subtle abnormalities in specific structures or functions in the brain.

Genetic and environmental factors appear to play a role in the disorder. Scientists believe that many genes on different chromosomes may be a cause. A research team recently identified a small gene region on chromosome 5 that may be associated with 15 percent of ASD cases (10). Another study found that abnormalities in a small region of chromosome 16 were about 100 times more common in children with ASDs than in unaffected children (11). Certain infections that occur before birth (such as rubella and cytomegalovirus) and older maternal age also have been associated with ASDs (2, 12).

About 10 percent of children with ASDs have other genetic diseases, including (1, 2):

  • Fragile X syndrome (intellectual disabilities and behavioral problems)
  • Tuberous sclerosis (non-cancerous tumors that affect the brain and other organs)
  • Down syndrome and other chromosomal birth defects

Do childhood vaccines contribute to ASDs?
Childhood vaccines, including the measles/mumps/rubella (MMR) vaccine, do not cause ASDs. Many studies have shown no link between the MMR vaccine and ASDs. In fact, the controversial 1998 study that set off concerns about a possible link between the MMR vaccine and ASDs was recently retracted by the medical journal Lancet that originally published it (13).

Some parents of children with autism suspected that the MMR vaccine, given around 12 to 15 months of age, contributed to ASDs because their children began to display symptoms of ASDs around the time they were vaccinated. Most likely, this is the age when symptoms of the disorder commonly begin, even if a child is not vaccinated.

Another reason that childhood vaccines were suspected of playing a role in ASDs is that, until recently, they contained a small amount of a preservative called thimerosal. Thimerosal contains mercury. While higher doses of certain forms of mercury may affect brain development, studies suggest that thimerosal does not. Since 2002, most routine childhood vaccines have not contained thimerosal. Some flu shots contain thimerosal, but parents can request flu shots that are thimerosal-free.

In 2004, an Institute of Medicine panel concluded, after reviewing many studies, that neither the MMR vaccine nor vaccines that contain thimerosal are associated with autism (14). A 2008 study found that the rate of ASDs in California continued to increase after thimerosal was removed from childhood vaccines, also suggesting a lack of association between thimerosal and ASDs (15).

How is autism treated?
Children often show great improvement with intensive behavioral treatment beginning during the preschool years. A recent study of children diagnosed with ASDs between the ages of 18 and 30 months found significant improvements in IQ (nearly 18 points), language skills and behavior after 2 years of participation in a behavioral intervention program designed for toddlers (16). The AAP recommends that infants and toddlers suspected of having an ASD be referred immediately to an early intervention program (2).

There is no cure for ASDs. However, some children benefit from medications that help improve their behavioral symptoms so that they are better able to learn. Some commonly used medications include:

  • Anti-depressants and anti-anxiety drugs.
  • Anti-psychotics: A new anti-psychotic drug called risperidone (Risperdal) is the only drug that is approved by the Food and Drug Administration (FDA) specifically for autistic behaviors, such as aggression, self-injury and temper tantrums (5).
  • Stimulants: One such medication is Ritalin, which is commonly prescribed for attention deficit hyperactivity disorder (ADHD).

Some children with ASDs are treated with alternative therapies, such as a strict eating plan, vitamins and detoxification therapies (such as the drug treatment called chelation which reduces the amount of mercury and other metals in the body). To date, there is no evidence to show these treatments are helpful (17). Parents who are interested in alternative treatments should discuss the possible risks and benefits with their child’s health care provider.

Does the March of Dimes support research on ASDs?
The March of Dimes supports a number of grantees who are studying the role of specific genes in brain development for insight into how abnormalities may cause ASDs. Study results could provide the basis for developing new treatments for ASDs. Another grantee is studying differences in how autistic children process information and pay attention, in order to develop improved educational interventions.

Where can I find more information on autism spectrum disorders?

  • Autism Spectrum Disorders (U.S. Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities)
  • Autism Fact Sheet (National Institute of Neurological Disorders and Stroke)
  • Autism (American Academy of Pediatrics)

References

  1. Centers for Disease Control and Prevention (CDC). (2009). Autism spectrum disorders.
  2. Johnson, C.P., Myers, S.M. and the Council on Children with Disabilities. (2007). Identification and evaluation of children with autism spectrum disorders. Pediatrics, 120 (5), 1183-1215.
  3. Centers for Disease Control and Prevention (CDC). (2009). Prevalence of autism spectrum disorders – autism and developmental disabilities monitoring network, United States, 2006. Morbidity and Mortality Weekly Report, 58 (SS-10).
  4. Kogan, M.A., Blumberg, S.J., Schieve, L.A., Boyle, C.A., Perrin, J.M., et al. (2009). Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the U.S., 2007. Pediatrics, 124 (5), 1395-1403.
  5. National Institute of Child Health & Human Development (2005). Autism Research at the NICHD.
  6. Limperopoulos, C., Bassan, H., Sullivan, N.R., Soul, J.S., Robertson, R.L., et al. (2008). Positive screening for autism in ex-preterm infants: prevalence and risk factors. Pediatrics, 121 (4), 758-765.
  7. Johnson, S., Hollis, C., Kochhar, P., Hennessy, E., Wolke, D., & Marlow, N. (2010). Autism spectrum disorders in extremely premature children. Journal of Pediatrics online.
  8. Kuban, K.C., O’Shea, T.M., Allred, E.N., Tager-Flusberg, H., Goldstein, D.J. & Leviton, A. (2009). Positive screening on the modified checklist for autism in toddlers (M-CHAT) in extremely low gestational age newborns. Journal of Pediatrics, 154 (4), 535-540.
  9. Buchmayer, S., Johansson, S., Johansson, A., Hultman, C.M., Sparen, P. & Cnattinguis, S. (2009). Can association between preterm birth and autism be explained by maternal or neonatal morbidity? Pediatrics, 124 (5), e817-825.
  10. Wang, K., Zhang, H., Ma, D., Bucan, M., Glessner, J.T., et al. (2009). Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature.
  11. Weiss, L.A., Shen, Y., Korn, J.M., Arking, D.E., Miller, D.T., et al. (2008). Association between microdeletion and microduplication at 16p11.2 and autism. New England Journal of Medicine, 358 (7), 667-675.
  12. Shelton, J.F., Tancredi, D.J. & Hertz-Picciotto. (2010). Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Research.
  13. Editors of The Lancet. (2010). Retraction—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet.
  14. Institute of Medicine. (2004). Immunization safety review: vaccines and autism. New York: National Academies Press.
  15. Schechter, R. & Grether, J. (2008). Continuing increases in autism reported to California’s developmental services system. Archives of General Psychiatry, 65 (1), 19-24.
  16. Dawson, G., Rogers, S., Munson, J., Smith, M., Winter, J., et al. (2010). Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver model. Pediatrics, 125 (1), e7-e23.
  17. Myers, S.M., Johnson, C.P., and the Council on Children with Disabilities. (2007). Management of children with autism spectrum disorders. Pediatrics, 120 (5), 1162-1182.

May 2010

Cerebral palsy

Cerebral palsy refers to a group of conditions that affect movement, balance and posture. Affected children have abnormalities in one or more parts of the brain that affect the ability to control muscles. Symptoms range from mild to severe but do not get worse as the child gets older. With treatment, most children can significantly improve their abilities.

Many children with cerebral palsy have other conditions that require treatment. These include intellectual disabilities, learning disabilities, seizures, abnormal physical sensations (difficulties with sense of touch), and problems with vision, hearing and speech.

How common is cerebral palsy?
Cerebral palsy usually is diagnosed by 3 years of age. About 2 to 3 children in 1,000 are affected (1). About 800,000 children and adults of all ages in the United States have cerebral palsy (2).

What are the different types of cerebral palsy?
There are three major types of cerebral palsy. Some individuals may have symptoms of more than one type.

  • Spastic cerebral palsy: About 70 to 80 percent of affected individuals have the spastic type, in which muscles are stiff, making movement difficult (1). Spastic diplegia is a form of spastic cerebral palsy in which both legs are affected. Affected children may have difficulty walking because tight muscles in the hips and legs cause legs to turn inward and cross at the knees (called scissoring). In spastic hemiplegia, only one side of the body is affected, often with the arm more severely affected than the leg. Most severe is spastic quadriplegia, in which all four limbs, the trunk and face are affected. Children with spastic quadriplegia usually cannot walk. They often have intellectual disabilities, difficulty speaking and seizures.
  • Athetoid or dyskinetic cerebral palsy: About 10 to 20 percent of affected individuals have the athetoid form, which affects the entire body (1). It is characterized by fluctuations in muscle tone (varying from too tight to too loose) and sometimes is associated with uncontrolled movements (which can be slow and writhing or rapid and jerky). Affected children often have trouble learning to control their bodies well enough to sit and walk. Because muscles of the face and tongue can be affected, there also can be difficulties with sucking, swallowing and speech.
  • Ataxic cerebral palsy: About 5 to 10 percent of affected individuals have the ataxic form, which affects balance and coordination (1). They may walk with an unsteady gait with feet far apart. They have difficulty with motions that require precise coordination, such as writing.

What are the causes of cerebral palsy?
Cerebral palsy usually is caused by factors that disrupt normal development of the brain before birth. In some cases, genetic defects may contribute to brain malformations and “miswiring” of nerve cell connections in the brain, resulting in cerebral palsy (2). Other cases are caused by injuries to the developing brain, such as a fetal stroke. Contrary to common belief, few cases of cerebral palsy are caused by a lack of oxygen reaching the fetus during labor and delivery (2).

A small number of babies develop brain injuries in the first months or years of life that can result in cerebral palsy (2). These injuries may be caused by brain infection (such as meningitis) and head injuries. In many cases, the cause of cerebral palsy in a child is not known.

Certain risk factors make it more likely that a baby will develop cerebral palsy. However, most babies with one of these risk factors do not develop cerebral palsy. Risk factors for cerebral palsy include:

  • Prematurity: Premature babies (those born before 37 completed weeks of pregnancy) who weigh less than 3 1/3 pounds are between 20 and 80 times more likely to develop cerebral palsy than full-term babies (3). Many of these tiny babies suffer from bleeding in the brain, which can damage delicate brain tissue, or develop periventricular leukomalacia, destruction of nerves around the fluid-filled cavities (ventricles) in the brain.
  • Infections during pregnancy: Certain infections in the mother can cause brain damage and result in cerebral palsy. Examples of these infections include rubella, cytomegalovirus (usually mild viral infection), herpes (viral infections that can cause genital sores), and toxoplasmosis (a usually mild parasitic infection). Maternal infections involving the placental membranes (chorioamnionitis) may contribute to cerebral palsy in full-term as well as premature babies (2). A 2003 study at the University of California at San Francisco found that full-term babies were 4 times more likely to develop cerebral palsy if they were exposed to chorioamnionitis in the womb (4).
  • Insufficient oxygen reaching the fetus: This may occur when the placenta is not functioning properly or it tears away from the wall of the uterus before delivery.
  • Asphyxia during labor and delivery: Until recently, it was widely believed that asphyxia (lack of oxygen) during a difficult delivery was the cause of most cases of cerebral palsy. Studies now show that birth complications, including asphyxia, contribute to only 5 to 10 percent of cases of cerebral palsy (2).
  • Severe jaundice: Jaundice, a yellowing of the skin and whites of the eyes, is caused by the build-up of a pigment called bilirubin in the blood. Mild cases of jaundice usually clear up without treatment and do not harm the baby. However, jaundice can occasionally become severe. Affected babies have high levels of bilirubin in the blood. Without treatment, high bilirubin levels can pose a risk of permanent brain damage, resulting in athetoid cerebral palsy. Certain blood diseases, such as Rh disease, can cause severe jaundice and brain damage, resulting in cerebral palsy. Rh disease is an incompatibility between the blood of the mother and her fetus. It usually can be prevented by giving an Rh-negative woman an injection of a blood product called Rh immune globulin around the 28th week of pregnancy and again after the birth of an Rh-positive baby.
  • Blood clotting disorders (thrombophilias): These disorders in either mother or baby may increase the risk of cerebral palsy.

What are some early signs of cerebral palsy?
Some children with cerebral palsy may have delays in learning to roll over, sit, crawl or walk. The Centers for Disease Control and Prevention (CDC) recommends that parents contact their child's provider if they see any of the following signs (5):

A child more than 2 months old who:

  • Has difficulty controlling her head when picked up
  • Has stiff legs that cross or “scissor” when picked up

A child more than 6 months old who:

  • Reaches with only one hand while keeping the other in a fist

A child more than 10 months old who:

  • Crawls by pushing off with one hand and leg while dragging the opposite hand and leg

A child more than 12 months old who:

  • Cannot crawl
  • Cannot stand with support

How is cerebral palsy diagnosed?
Cerebral palsy is diagnosed mainly by evaluating how a baby or young child moves. The provider evaluates the child's muscle tone; children with cerebral palsy may appear floppy or stiff. Some may have variable muscle tone (too loose at times and too tight at other times).

The provider checks the child's reflexes and look to see if the baby has developed a preference for using his right or left hand. While most babies do not develop a hand preference (become right- or left-handed) until at least 12 months of age, some babies with cerebral palsy do so before 6 months of age.

Another important sign of cerebral palsy is the persistence of certain reflexes, called primitive reflexes. These reflexes are normal in younger infants but generally disappear by 6 to 12 months of age. The provider also takes a careful medical history and attempts to rule out any other disorders that could be causing the symptoms.

The provider may suggest brain imaging tests, such as magnetic resonance imaging (MRI), computed tomography (CT scan) or ultrasound. These tests sometimes can help identify the cause of cerebral palsy. Ultrasound often is recommended in premature babies who are considered at risk for cerebral palsy to help diagnose brain abnormalities that are frequently associated with cerebral palsy. In some children with cerebral palsy, especially those who are mildly affected, brain imaging tests show no abnormalities, suggesting that microscopically small areas of brain damage can cause symptoms.

About half of babies who are suspected to be at higher risk for cerebral palsy at 12 months of age appear to outgrow their symptoms by age 2 (6).

How is cerebral palsy treated?
A team of health care professionals works with the child and family to identify the child's needs and create an individualized treatment plan to help the child reach his or her maximum potential. The team is generally coordinated by one health care professional and may include pediatricians, physical medicine and rehabilitation physicians, orthopedic surgeons, physical and occupational therapists, ophthalmologists (eye doctors), speech/language pathologists, social workers and psychologists.

The child usually begins physical therapy soon after diagnosis. Therapy improves motor skills (such as sitting and walking) and muscle strength and helps prevent contractures (shortening of muscles that limits joint movement). Sometimes braces, splints or casts are used along with physical therapy to help prevent contractures and to improve function of the hands or legs. If contractures are severe, surgery may be recommended to lengthen affected muscles.

Drugs sometimes are recommended to ease spasticity or to reduce abnormal movement. Unfortunately, oral drug treatment often is not very helpful. Sometimes injection of drugs, such as Botox (botulinum toxin), directly into spastic muscles is helpful. The effects may last several months.

A new type of drug treatment is showing promise in children with moderate to severe spasticity. During a surgical procedure, a pump is implanted under the skin that continuously delivers the anti-spasmodic drug baclofen.

For some children with spastic cerebral palsy, a surgical technique called selective dorsal rhizotomy may permanently reduce spasticity and improve the ability to sit, stand and walk. In this procedure, doctors identify and cut some of the nerve fibers at the base of the spine that are contributing most to spasticity. This procedure usually is recommended only for children with severe spasticity who have not responded well to other treatments (2).

Occupational therapists work with the child on skills required for daily living, including feeding and dressing. Children with speech problems work with a speech therapist or, in more severe cases, learn to use a computerized voice synthesizer that can speak for them. Computers have become an important tool for children and adults with cerebral palsy in terms of therapy, education, recreation and employment.

Some children with cerebral palsy may benefit from the many mechanical aids available today, including walkers, positioning devices (to allow a child with abnormal posture to stand correctly), customized wheelchairs, and specially adapted scooters and tricycles.

Can cerebral palsy be prevented?
In many cases, the cause of cerebral palsy is not known, so there is nothing that can be done to prevent it. However, some causes of cerebral palsy can be prevented by eliminating or managing certain risk factors.

Rh disease and congenital rubella syndrome used to be common causes of cerebral palsy. Now Rh disease usually can be prevented when an Rh-negative pregnant woman receives appropriate care. Women can be tested for immunity to rubella before pregnancy and vaccinated if they are not immune. A woman can help reduce her risk of preterm delivery when she seeks early (ideally starting with a preconception visit) and regular prenatal care and avoids cigarettes, alcohol and illicit drugs.

Babies with severe jaundice can be treated with special lights (phototherapy) and blood transfusions (exchange transfusions), when indicated. Head injuries in babies and young children often can be prevented when babies ride in car seats properly positioned in the back seat of the car and when children wear helmets when riding bicycles. Routine vaccination of babies (with the Hib vaccine) prevents many cases of meningitis, another cause of brain damage in the early months.

Is the March of Dimes conducting research on cerebral palsy?
The March of Dimes supports a number of grants on prenatal brain development and factors that may disrupt it.

One grantee is studying how developing nerve cells in the fetal brain respond to prolonged oxygen deprivation. This can improve understanding of how lack of oxygen before or around the time of birth can injure the developing brain and how such brain injuries can be prevented or treated.

Another grantee is investigating how intrauterine infections may contribute to brain injuries that result in cerebral palsy, with the goal of developing drug treatments to help prevent these injuries.

A grantee also is studying specific learning disabilities in young children with cerebral palsy in order to develop improved interventions.

Many other March of Dimes grantees are seeking improved ways of preventing preterm delivery, an important risk factor for cerebral palsy.

For further information
Cerebral Palsy, Centers for Disease Control and Prevention (CDC)

References

  1. Centers for Disease Control and Prevention (CDC). Cerebral Palsy. October 4, 2004, accessed September 14, 2007.
  2. National Institute of Neurological Disorders and Stroke. Cerebral Palsy: Hope Through Research. NIH Publication Number 06-159, updated 7/13/07.
  3. Platt, M., et al. Trends in Cerebral Palsy Among Infants of Very Low Birthweight (<1500 g) or Born Prematurely (<32 Weeks) in 16 European Centres: A Database Study. Lancet, volume 369, January 6, 2006, pages 43-50.
  4. Wu, Y.W., et al. Chorioamnionitis and Cerebral Palsy in Term and Near-Term Infants. Journal of the American Medical Association, volume 290, number 20, November 26, 2003, pages 2677-2684.
  5. Centers for Disease Control and Prevention (CDC). Learn the Signs, Act Early: Cerebral Palsy Fact Sheet. December 7, 2006.
  6. Pellegrino, Louis. Cerebral palsy, in Batshaw, M.L. (ed.), Children With Disabilities, Fifth Edition, Baltimore, MD, Paul H. Brooks Publishing Company, 2002, pages 433-466.

December 2007

Chromosomal conditions

Babies with chromosomal conditions have a problem in one or more of their chromosomes. Chromosomes are the structures that hold genes. Genes are part of your body's cells that store instructions for the way your body grows and works. Genes are passed from parents to children.

Each person has 23 pairs of chromosomes, or 46 in all. For each pair, you get one chromosome from your mother and one chromosome from your father.

About 1 in 150 babies is born with a chromosomal condition. Down syndrome is an example of a chromosomal condition. Because chromosomes and genes are so closely related, chromosomal conditions are also called genetic conditions.

What causes chromosomal conditions?
Chromosomal conditions are caused by two kinds of changes in chromosomes: 

  1. Changes in the number of chromosomes—This means you have too many or too few chromosomes.
  2. Changes in the structure of chromosomes—This means that part of a chromosome may be missing, repeated or rearranged.

Both kinds of changes can be inherited. This means they’re passed from parent to child. Or they can happen randomly as cells develop.

What problems can chromosomal conditions cause?
Sometimes chromosomal conditions can cause miscarriage. This is when a baby dies in the womb before 20 weeks of pregnancy. More than half of miscarriages are caused by chromosomal conditions. These conditions also can cause stillbirth, which is when a baby dies in the womb before birth but after 20 weeks of pregnancy.

Each child born with a chromosomal condition is different. Some children with chromosomal conditions have intellectual disabilities or birth defects, or both. Some children with these conditions don’t have any serious problems. The problems depend on which chromosomes are affected and how.

How do you know if your baby has a chromosomal condition?
The American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women be offered prenatal tests for Down syndrome and other chromosomal conditions. A screening test is a medical test to see if you or your baby is more likely than others to have a certain health condition.

You can have screening tests in the first or second trimester of pregnancy. First trimester screening is done at 11 to 13 weeks of pregnancy. Along with a blood test, you get a special ultrasound that checks the back of your baby’s neck. Testing in the second trimester is called maternal blood screening. You can get this blood test between 15 and 20 weeks of pregnancy.

If a screening test shows that your baby may have a problem, your provider gives you a diagnostic test. This is a medical test to see if you do or don't have a certain health condition. Diagnostic tests include amniocentesis or chorionic villus sampling. Your provider also can check your baby’s blood for chromosomal conditions after he’s born.

What are the chances of your baby having a chromosomal condition?
As you get older, there’s a greater chance of having a baby with certain chromosomal conditions, like Down syndrome. For example, at age 35, your chances of having a baby with a chromosomal condition are 1 in 192. At age 40, your chances are 1 in 66.

If you or someone in your family has a chromosomal condition, or if you have a baby with a chromosomal condition, talk to a genetic counselor. A genetic counselor is a person who is trained to know about genetics, birth defects and other medical problems that run in families. She can help you understand the causes of chromosomal conditions, what kind of testing is available, and your chances of having a baby with these conditions. If you already have a baby with a chromosomal condition, the chances of having another baby with the same condition are usually low.

For more information
Chromosome Disorder Outreach
Genetic Alliance
National Down Syndrome Society
National Organization for Rare Disorders

Last reviewed February 2013

See also: Birth defects, Genetic counseling,Your family health history

Cleft lip and cleft palate

A cleft lip is a birth defect in which a baby's upper lip doesn’t form completely and has an opening in it. A cleft palate is a similar birth defect in which a baby’s palate (roof of the mouth) doesn’t form completely and has an opening in it. These birth defects are called oral clefts.

How does a cleft lip affect a baby’s face?
Some babies with cleft lip have just a small notch in the upper lip. Others have a complete opening or hole in the lip that goes through the upper gum to the bottom of the nose. A cleft lip can happen on one or both sides of a baby’s mouth.

How does a cleft palate affect a baby’s mouth?
A cleft palate can affect the soft palate (the soft tissue at the back of the roof of the mouth) or the hard palate (the bony front part of the roof of the mouth). A cleft palate can happen on one or both sides of a baby’s palate.

Do cleft lip and cleft palate always happen together?
No. Some babies have just a cleft lip. But most babies with a cleft lip also have a cleft palate. Some babies have only a cleft palate, which is called an isolated cleft palate.

What problems can oral clefts cause?
Babies and children with oral clefts may have:

When do oral clefts happen?
Oral clefts happen very early in pregnancy. Your baby’s lips are formed by about 6 weeks of pregnancy. Your baby’s palate is formed by about 10 weeks of pregnancy. Oral clefts happen when your baby’s lips or palate or both don’t form completely.

What causes oral clefts?
We’re not sure what causes oral clefts. Some possible causes are:

  • Changes in your baby’s genes. Genes are part of your baby’s cells that store instructions for the way the body grows and works. They provide the basic plan for how your baby develops. Genes are passed from parents to children.
  • Not getting enough folic acid before pregnancy. Folic acid is a vitamin that can help protect your baby from birth defects of the brain and spine called neural tube defects. It also may reduce the risk of oral clefts by about 25 percent.
  • Taking certain medicines, like anti-seizure medicine, during pregnancy
  • Smoking during pregnancy. Smoking causes 1 in 5 (20 percent) oral clefts.
  • Drinking alcohol during pregnancy
  • Having certain infections during pregnancy

Can oral clefts be prevented?
Not all clefts can be prevented. But there are things you can do to help reduce your chances of having a baby with an oral cleft:

  • Before pregnancy, get a preconception checkup. This is a medical checkup to help make sure you are healthy before you get pregnant.
  • Before pregnancy, take a multivitamin with 400 micrograms of folic acid in it every day.
  • During pregnancy, take a prenatal vitamin with 600 micrograms of folic acid in it every day.
  • Talk to your provider to make sure any medicine you take is safe during pregnancy.
  • Your provider may want to switch you to a different medicine that is safe during pregnancy.
  • Don’t smoke.
  • Don’t drink alcohol.
  • Get early and regular prenatal care.

How are oral clefts treated?
In most cases, oral clefts can be repaired by surgery. Each baby is unique, but surgery to repair cleft lip usually is done at 10 to 12 weeks of age. Surgery for cleft palate usually is done between 9 and 18 months of age. Your child may need more surgery for oral clefts as he grows.

Your baby gets treated by a team of specialists. Most teams include:

  • Pediatrician. This is a doctor who has special training in taking care of babies and children.
  • Plastic surgeon. This is a doctor who repairs or rebuilds parts of the body to improve how they work and look.
  • Pediatric dentist. This is a dentist who has special training to care for the teeth of babies and children.
  • Orthodontist. This is a dentist who fixes tooth defects and straightens teeth with braces and other methods.
  • Otolaryngologist or ear, nose and throat specialist (also called ENT). This is a doctor who treats problems of the ears, nose and throat.
  • Speech or language specialist. This is a person trained to help with speech problems.
  • Audiologist. This is a person trained to measure hearing loss and fit hearing aids.
  • Genetic counselor. This is a person trained to know about genetics, birth defects and other medical problems that run in families.
  • Social worker. This is a person trained to help find resources and programs, such as health care and special services, for people with disabilities.

How common are oral clefts?
About 6,800 babies in the United States are born with oral clefts each year.

  • Cleft lip and cleft palate affects about 4,200 babies each year. It is more common in Asians and certain Native Americans.
  • Nearly 2,600 babies are born with isolated cleft palate each year. Isolated cleft palate affects babies of all races about the same.

Can other birth defects happen along with oral clefts?
Yes. There are about 400 health conditions (called syndromes) that are related to oral clefts. If your baby has an oral cleft, his provider checks him thoroughly for other birth defects soon after birth.

Are oral clefts more common in some families?
Yes. If you have family members with oral clefts, you may be more likely to have a baby with an oral cleft. If neither you nor your partner has a cleft but your baby does, and if your baby doesn’t have any kind of syndrome, the chance of you having another baby with a cleft is about 2 to 5 out of 100 (2 to 5 percent).

If you have a family history of oral clefts, or if you’ve had a baby with oral cleft, you can meet with a genetic counselor to find out the chances of having a baby with oral cleft. To find a genetic counselor, you can ask your provider or contact the National Society of Genetic Counselors.

For more information
Cleft Palate Foundation

Clubfoot

Clubfoot (also called talipes equinovarus) is a birth defect of the foot. Birth defects are health conditions that are present at birth. Birth defects change the shape or function of one or more parts of the body. They can cause problems in overall health, how the body develops or in how the body works.

If your baby has clubfoot, one foot or both feet point down and turn in. This happens because the tissues that connect muscles to bone (called tendons) in your baby’s leg and foot are shorter than usual. This pulls the foot into an abnormal position. Babies with clubfoot also may have abnormal foot bones, ankle joints and muscles.

Clubfoot is a common birth defect. About 1 in 1,000 babies is born with clubfoot in the United States each year.

What problems does clubfoot cause?
Clubfoot can range from mild to serious. Clubfoot isn’t painful, and it doesn’t bother your baby until he begins to stand and walk. If it’s not treated, he may have problems walking correctly. For example, he may walk on the sides of his feet or even on the tops of his feet instead of on the bottoms or soles of the feet. Sometimes, the part of the foot he walks on abnormally can get infected, and the skin can get thick and hard. Clubfoot that’s not treated can cause arthritis. This is a health condition that causes joint pain, aches, stiffness and swelling.

How do you know if your baby has clubfoot?
Your baby’s provider can identify clubfoot and other foot problems in a physical exam of your baby after birth. Your baby’s provider may use other tests, like a foot X-ray.

Sometimes, your health care provider may see that your baby has clubfoot before birth using ultrasound. An ultrasound uses sound waves and a computer screen to make a picture of your baby in the womb. Even though clubfoot can’t be treated until your baby is born, knowing about it while you’re pregnant may help you plan ahead for treatment.

How is clubfoot treated?
A doctor with special training in bone conditions called an orthopedic surgeon can help you understand the best treatment for your baby. Until recently, many children with clubfoot had surgery to correct their condition. Now, most children with clubfoot can be treated without surgery. Treatment works best when it’s started early, even as early as 1 week old. With early treatment, most children with clubfoot can grow up to wear regular shoes and have active, normal lives.

Clubfoot treatment may include:

  • Stretching and casting (also called the Ponseti method). This is the most common treatment for clubfoot. It usually starts in the first 2 weeks of your baby’s life.For this treatment, your baby’s provider stretches your baby’s foot toward the correct position and then puts it in a cast. The cast goes from your baby’s toes to his upper thigh. Every 4 to 7 days, your baby’s provider takes off the cast, moves your baby’s foot closer to the correct position and puts on a new cast. Before your baby gets his last cast, his provider may cut the heel cord. This is the tendon that connects the heel to muscles in your baby’s calf. This allows the heel cord to grow to a normal length by the time the last cast comes off.This type of treatment usually fixes the problem in 2 to 3 months. After that, your baby can do stretching exercises to help keep his feet in the right position. He also may need to wear special shoes or a brace at night for a few years.
  • Stretching, taping and splinting (also called the French method). With this treatment, your baby’s provider stretches your baby’s foot toward the correct position and uses tape and splints to hold it that way. This treatment usually starts soon after birth and is done every day for 2 months and then less often until your baby is 6 months old. After this, you can use stretching exercises and night splints to help keep your baby’s feet in the right position until she starts to walk.
  • Surgery. If your baby’s clubfoot is severe or if stretching treatments don’t work, clubfoot can be treated with surgery. It’s best to have surgery before your baby starts walking. Surgery can help make the heel cord longer and fix other problems with the feet. After surgery, your baby may be in a cast for 6 to 8 weeks.

What causes clubfoot?
We don’t know what causes clubfoot, and there’s no way to prevent it. But some things may make a baby more likely than others to have the condition, including:

  • Your baby is a boy. Boys are twice as likely as girls to have clubfoot.
  • Your baby has another birth defect, like cerebral palsy or spina bifida.
  • You have clubfoot in your family health history. This is a record of any health conditions and treatments that you, your partner and everyone in your families have had. If you, your partner or one of your children has clubfoot, your baby’s risk of having clubfoot increases. If you already have a baby with clubfoot, your chances of having another baby with the condition is about a 2 in 50 (about 4 percent). You can talk to a genetic counselor to help you understand the chances of having another baby with clubfoot. A genetic counselor is a person who is trained to know about genetics, birth defects and other medical problems that run in families.
  • You have oligohydramnios during pregnancy. This is when you don’t have enough amniotic fluid. This is the fluid that surrounds your baby in the womb.
  • You have an infection or use street drugs or smoke during pregnancy. Don’t smoke or take street drugs during pregnancy.

Last reviewed January 2013

See also: Your family health history, Genetic counseling

Congenital heart defects

About 35,000 infants (1 out of every 125) are born with heart defects each year in the United States (1). The defect may be so slight that the baby appears healthy for many years after birth, or so severe that his life is in immediate danger.

Heart defects are among the most common birth defects and are the leading cause of birth defect-related deaths (2). However, advances in diagnosis and surgical treatment have led to dramatic increases in survival for children with serious heart defects. In the United States, about 1.4 million children and adults live with congenital heart defects today (3). Almost all are able to lead active, productive lives (1).

What is a congenital heart defect?
A congenital heart defect is an abnormality in any part of the heart that is present at birth. Heart defects originate in the early weeks of pregnancy when the heart is forming.

How does the heart work?
The heart is a muscle that pumps blood to the body. It is divided into four hollow parts called chambers. Two chambers are located on the right side of the heart, and two are on the left. Within the heart are four valves (one-way openings) that let the blood go forward and keep it from going back. Blood goes from the heart to the lungs where it picks up oxygen. From the lungs, the blood carrying oxygen, which appears bright red, goes back to the heart. The heart then pumps the oxygen-rich blood through the body by way of arteries. As the oxygen is used up by the body's tissues and organs, the blood becomes dark and returns by way of veins to the heart, where the process starts over again.

How do heart defects affect a child?
Some babies and children with heart defects experience no symptoms. The heart defect may be diagnosed if the health care provider hears an abnormal sound, called a murmur. Children with normal hearts also can have heart murmurs, called innocent or functional murmurs. A provider may suggest tests to rule out a heart defect.

Certain heart defects can cause congestive heart failure.
In this condition, the heart can’t pump adequate blood to the lungs or other parts of the body. It can lead to fluid build-up in the heart, lungs and other parts of the body. An affected child may experience a rapid heartbeat and breathing difficulties, especially during exercise. Infants may experience these difficulties during feeding, sometimes resulting in poor weight gain. Affected infants and children also may have swelling of the legs or abdomen or around the eyes.

Some heart defects result in a pale grayish or bluish coloring of the skin called cyanosis. This usually appears soon after birth or during infancy and should be evaluated immediately by a health care provider. On occasion, cyanosis may be delayed until later in childhood. Cyanosis is a sign of defects that prevent the blood from getting enough oxygen. Children with cyanosis may tire easily. Symptoms, such as shortness of breath and fainting, often worsen when the child exerts himself. Some youngsters may squat frequently to ease their shortness of breath.

What tests are used to diagnose heart defects?
Babies and children who are suspected of having a heart defect are usually referred to a pediatric cardiologist (children’s heart disease specialist). This doctor can do a physical examination and often recommends one or more of the following tests:

  • Chest X-ray
  • Electrocardiogram, a test that records heart rate patterns
  • Echocardiogram, a special form of ultrasound that uses sound waves to take pictures of the heart

All of these tests are painless and noninvasive (nothing enters the child’s body). Some children with heart disease also may need to undergo a procedure called cardiac catheterization. In this procedure, a thin, flexible tube is inserted into the heart after the child is given medications to make him sleepy. This test provides detailed information about the heart and how it is working.

What causes congenital heart defects?
In most cases, scientists do not know what makes a baby's heart develop abnormally. Genetic and environmental factors appear to play roles.

Scientists are making progress in understanding the genetics of heart defects. Since the 1990s, they have identified about 10 gene mutations (changes) that can cause isolated (not accompanied by other birth defects) heart defects (3). For example, a March of Dimes grantee identified a gene that can cause a heart defect called an atrial septal defect (a hole between the upper chambers of the heart), and one that may contribute to hypoplastic left heart syndrome (underdevelopment of the heart’s main pumping chamber) (4, 5).

Environmental factors can contribute to congenital heart defects. Women who contract rubella (German measles) during the first three months of pregnancy have a high risk of having a baby with a heart defect. Other viral infections, such as the flu, also may contribute, as may exposure to certain industrial chemicals (solvents) (2). Some studies suggest that drinking alcohol or using cocaine in pregnancy may increase the risk of heart defects (2).

Certain medications increase the risk. These include (2):

  • The acne medication isotretinoin (Accutane and other brand names)
  • Thalidomide (approved only for a rare, severe skin disorder, but sometimes used for other conditions)
  • Certain anti-seizure medications

Some studies suggest that first-trimester use of trimethoprim-sulfonamide (a combination of antibiotics sometimes used to treat urinary-tract infections) may increase the risk of heart defects (2).

Certain chronic illnesses in the mother, such as diabetes, may contribute to heart defects (2). However, women with diabetes can reduce their risk by making sure their blood sugar levels are well controlled before becoming pregnant.

Heart defects can be part of a wider pattern of birth defects. For example, at least 30 percent of children with chromosomal abnormalities, such as Down syndrome (intellectual disabilities and physical birth defects) and Turner syndrome (short stature and lack of sexual development), have heart defects (3). Children with Down syndrome, Turner syndrome and certain other chromosomal abnormalities should be routinely evaluated for heart defects.

Heart defects also are common in children with a variety of inherited disorders, including Noonan syndrome (short stature, learning disabilities), velocardiofacial syndrome (craniofacial defects and immune deficiencies), Holt-Oram syndrome (limb defects) and Alagille syndrome (liver, skeletal and eye defects) (3).

What are some of the most common heart defects, and how are they treated?

  • Patent ductus arteriosus (PDA): Before birth, a large artery (ductus arteriosus) lets the blood bypass the lungs because the fetus gets its oxygen through the placenta. The ductus normally closes soon after birth so that blood can travel to the lungs and pick up oxygen. If it doesn’t close, the baby may develop heart failure. This problem occurs most frequently in premature babies. Treatment with medicine during the early days of life often can close the ductus. If that doesn't work, surgery is needed.
  • Septal defect: This is a hole in the wall (septum) that divides the right and left sides of the heart. A hole in the wall between the heart’s two upper chambers is called an atrial septal defect, while a hole between the lower chambers is called a ventricular septal defect. These defects can cause the blood to circulate improperly, so the heart has to work harder. Some atrial septal defects can be repaired without surgery by inserting a thin, flexible tube into the heart and then releasing a device that plugs the hole. A surgeon also can close an atrial or ventricular septal defect by sewing or patching the hole. Small holes may heal by themselves or not need repair at all.
  • Coarctation of the aorta: Part of the aorta, the large artery that sends blood from the heart to the rest of the body, may be too narrow for the blood to flow evenly. A surgeon can cut away the narrow part and sew the open ends together, replace the constricted section with man-made material, or patch it with part of a blood vessel taken from elsewhere in the body. Sometimes, this narrowed area can be widened by inflating a balloon on the tip of a catheter (tube) inserted through an artery.
  • Heart valve abnormalities: Some babies are born with heart valves that do not close normally or are narrowed or blocked, so blood can’t flow smoothly. Surgeons usually can repair the valves or replace them with man-made ones. Balloons on catheters also are frequently used to fix faulty valves.
  • Tetralogy of Fallot: This combination of four heart defects keeps some blood from getting to the lungs. As a result, the blood that is pumped to the body may not have enough oxygen. Affected babies have episodes of cyanosis and may grow poorly. This defect is usually surgically repaired in the early months of life.
  • Transposition of the great arteries: Transposition occurs when the positions of the two major arteries leaving the heart are reversed, so that each arises from the wrong pumping chamber. Affected newborns suffer from severe cyanosis due to a lack of oxygen in the blood. Recent surgical advances make it possible to correct this serious defect in the newborn period.
  • Hypoplastic left heart syndrome: This combination of defects results in a left ventricle (the heart’s main pumping chamber) that is too small to support life. Without treatment, this defect is usually fatal in the first few weeks of life. However, over the last 25 years, survival rates have dramatically improved with new surgical procedures and, less frequently, heart transplants (6).

At what age do children have surgery to repair heart defects?
Many children who require surgical repair of heart defects now undergo surgery in the first months of life. Until recently, it was often necessary to make temporary repairs and postpone corrective surgery until later in childhood. Now, early corrective surgery often prevents development of additional complications and allows the child to live a normal life.

Following surgery, children should have periodic heart checkups with a cardiologist. Children and adults with certain heart defects, even after surgical repair, remain at increased risk of infection involving the heart and its valves. Parents of children with heart defects and adults with repaired heart defects should discuss with their provider whether they need to take antibiotics before dental visits and other procedures to prevent these infections. Antibiotic treatment is recommended only for those considered at highest risk for infection, including those with man-made heart valves (7).

Is there a prenatal test for congenital heart defects?
Echocardiography can be used before birth to accurately identify many heart defects. If this test shows that a fetus’s heart is beating too fast or too slowly (called an arrhythmia), the mother can be treated with medications that may restore a normal heart rhythm in the fetus. This treatment often prevents fetal heart failure. In other cases, where the heart defect can't be treated before birth, parents and providers can plan the delivery so that the baby can receive necessary evaluation and treatment soon after birth.

Can congenital heart defects be prevented?
Most congenital heart defects cannot be prevented. However, there are some steps a woman can take before and during pregnancy that may help reduce the risk of having a baby with a heart defect:

  • Take a multivitamin containing 400 micrograms of folic acid daily, starting before pregnancy. This helps to prevent serious birth defects of the brain and spinal cord and may also help prevent heart defects.
  • Go for a preconception visit with her health care provider. At this visit, a woman should be tested for immunity to rubella and be vaccinated if she is not immune. Women with chronic health conditions, such as diabetes and phenylketonuria (PKU), should discuss adjusting their medications and/or eating habits to keep these conditions under control before and during pregnancy.
  • Discuss all medications with their provider, even over-the-counter or herbal medicines.
  • Avoid people who have the flu or other illnesses with fever.
  • Avoid exposure to organic solvents, used in products such as paints, varnishes and degreasing/cleaning agents.

Are heart defects likely to recur in another pregnancy?
Parents who have already had a child with a heart defect do have an increased risk of having other affected children, often with the same heart defect. In many cases, the risk is low. Some heart defects have about a 2 to 3 percent chance of happening again (8). However, the risk may differ, depending on the specific heart defect. If a child’s heart defect is part of a syndrome of other birth defects, the recurrence risk in another pregnancy may be much higher.

Parents who have had a child with a heart defect should consult their pediatric cardiologist and can consult a genetic counselor to find out the risks to any future children. Parents who themselves have a heart defect also are at increased risk of having an affected child and should consider consulting a genetic counselor.

Is pregnancy safe for women with heart defects?
Many women with congenital heart defects can safely become pregnant and have healthy babies. However, women with congenital heart defects always should check with their cardiologist before they become pregnant. Pregnancy can be risky for women with certain types of heart disease (including those with poorly functioning ventricles or high blood pressure in the lungs) (9).

In some cases, the mother’s heart disease or the medications she takes to treat it can affect the fetus, causing poor growth, premature delivery or other problems (9). Some women with heart disease may need careful monitoring by a high-risk obstetrician, as well as their cardiologist, throughout pregnancy.

Does the March of Dimes support research on congenital heart defects?
A number of scientists funded by the March of Dimes are studying genes that may underlie specific heart defects or seeking to identify new genes that may cause heart defects. The goal of this research is to better understand the causes of congenital heart defects, in order to develop ways to prevent them. Grantees also are looking at how environmental factors (such as a form of vitamin A called retinoic acid) may contribute to congenital heart defects. One grantee is seeking to understand why some babies with serious heart defects develop brain injuries, in order to learn how to prevent and treat them.

For additional information on congenital heart defects:

References

  1. National Heart, Lung and Blood Institute. Congenital Heart Defects. December 2007.
  2. Congenital Cardiovascular Defects: Current Knowledge: A Scientific Statement From the American Heart Association Council on Cardiovascular Disease in the Young. Circulation, volume 115, June 12, 2007, pages 2995-3014.
  3. Pierpont, M.E., et al. Genetic Basis for Congenital Heart Defects: Current Knowledge: A Scientific Statement From the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young. Circulation, volume 115, June 12, 2007, pages 3015-3038.
  4. Garg, V., et al. GATA4 Mutations Cause Human Congenital Heart Defects and Reveal an Interaction with TBX5. Nature, volume 424, July 24, 2003, pages 443-447.
  5. Garg, V., et al. Mutations in NOTCH1 Cause Aortic Valve Disease. Nature, volume 437, September 8, 2005, pages 270-274.
  6. Johnston, M.V. Congenital Heart Disease and Brain Injury. New England Journal of Medicine, volume 357, number 19, November 2, 2007, pages 1971-1973.
  7. American Heart Association. Congenital Heart Defects. Accessed 3/24/08.
  8. Gill, H.K., et al. Patterns of Recurrence of Congenital Heart Disease. Journal of the American College of Cardiology, volume 42, number 5, September 3, 2003, pages 923-929.
  9. Uebing, A., et al. Pregnancy and Congenital Heart Disease. British Medical Journal, volume 332, February 18, 2006, pages 401-406.

May 2008

Cystic fibrosis and your baby

Cystic fibrosis (CF) is a condition that affects breathing and digestion. It’s caused by very thick mucus that builds up in the body.

Mucus is a fluid that normally coats and protects parts of the body. It’s usually slippery and slightly thinker than water. But in CF, the mucus is thicker and sticky. It builds up in the lungs and digestive system and can cause problems with how you breathe and digest food.

CF affects about 30,000 children and adults in the United States. It is one of the most common genetic conditions in this country. About 1 in 3,500 babies is born with CF.

What causes CF?
CF is inherited. This means it’s passed from parent to child through genes. A gene is a part of your body’s cells that stores instructions for the way your body grows and works. Genes come in pairs—you get one of each pair from each parent.

Sometimes the instructions in genes change. This is called a gene change or a mutation. Parents can pass gene changes to their children. Sometimes a gene change can cause a gene to not work correctly. Sometimes it can cause birth defects or other health conditions. A birth defect is a health condition that is present in a baby at birth.

Your baby has to inherit a gene change for CF from both parents to have CF. If she inherits the gene change from just one parent, she has the gene change for CF, but she doesn’t have the condition. When this happens, your baby is called a CF carrier. A CF carrier has the gene but doesn’t have the condition.

What problems does CF cause?
Babies with CF have very thick and sticky mucus that builds up in the body. When this mucus builds up in the lungs, it blocks airways and causes breathing problems and infections. Airways are tubes that carry air in and out of the lungs. As a baby with CF gets older, lung infections can get worse. This can lead to serious, and sometimes deadly, lung damage.

When mucus builds up in the digestive system, it blocks tubes in the pancreas, an organ in the belly. This can make it hard for the body’s digestives system to break down food. When this happens, your baby may not get the nutrients she needs to grow and stay healthy.

Some cases of CF are more serious than others. Babies with CF are often sick with infections and need a lot of special medical care.

How do you know if your baby has CF?
All babies have newborn screening tests for CF. Newborn screening checks for serious but rare and mostly treatable conditions at birth. It includes blood, hearing and heart screening. With newborn screening, CF can be found and treated early.

Before your baby leaves the hospital, his health care provider takes a few drops of blood from his heel to test for CF and other conditions. The blood is collected and dried on a special paper and sent to a lab for testing. The lab then sends the results back to your baby’s provider.

If newborn screening results aren’t normal, it simply means your baby needs more testing. Your baby’s provider can recommend another kind of test, called a diagnostic test. This test can check to see if your baby has CF or if there is some other cause for abnormal test results.

Your provider may recommend that your baby have a sweat test to see if he has CF. This is a simple, painless test that checks the amount of salt in your baby’s sweat. Babies with CF have more salt in their sweat than healthy babies. Your baby’s provider also may recommend a genetic test for your baby.

If your baby does have CF, he may have these signs and symptoms that can be mild or serious:

  • Coughing or wheezing
  • Having lots of mucus in the lungs
  • Many lung infections, like pneumonia and bronchitis
  • Shortness of breath
  • Salty skin
  • Slow growth, even with a big appetite
  • Meconium ileus, when meconium gets stuck in a newborn’s intestine. Meconium is a baby's first bowel movement. It can be green, brown or black in color.
  • Bowel movements that are frequent, loose, large or look greasy
  • Stomach pain or bloating

If your baby has CF, how are lung and breathing problems treated?
Many lung infections in babies with CF are caused by bacteria that don’t usually cause problems for healthy babies. If your baby has CF, medicines like antibiotics often cannot get rid of all the bacteria in his lungs. These infections can lead to lung damage.

Your child’s treatment depends on the kind of symptoms he has and how severe they are. Certain medicines can help children with CF breathe better and prevent infections. Some come as a mist that your child breathes into the lungs. Medicines used for CF include:

  • Mucus-thinners. Medicines like PulmozymeÒ (Dnase) help thin mucus, making it easier to cough out.
  • Bronchodilators. These medicines help open the airways to clear mucus from the lungs. Examples are AlbuterolÒ, ProventilÒ and VentolinÒ.
  • Antibiotics. These are medicines that kill infections caused by bacteria. TOBIÒ (tobramycin) is a common inhaled antibiotic, and azithromycin is a common antibiotic taken by mouth.
  • Ibuprofen. This medicine can help reduce lung redness and swelling that make breathing difficult.
  • Hypertonic saline. Inhaling this salt-water mist helps draw more water into the airways. This helps thin the mucus.

Your child’s provider may recommend that she gets lots of physical activity or that you use other therapies to vibrate (shake) the chest to help loosen mucus in her lungs. This can make it easier for your child to cough mucus up and out of the lungs.

If your child’s CF becomes life-threatening, a lung transplant may be an option. This is a major operation that is becoming more successful in treating CF.

If your baby has CF, how are growth and digestion problems treated?
Some children with CF gain weight and grow normally. But many grow more slowly than other children.

Most children with CF need to take special medicines that help their bodies get nutrients from food. This helps with weight gain and digestion.

To help them grow, children with CF need healthy, high-calorie meals. They need extra vitamins, especially vitamins A, D, E and K. A dietitian with experience in treating children with CF can help you create your child’s meal plan for a healthy weight gain. A dietician is a person with special training in helping people eat healthy.

Some teens or young adults with CF may get CF-related diabetes. This is usually treated by getting shots of insulin at meal times. It’s important to keep diabetes under control so that it doesn’t cause more lung problems.

For more information
Cystic Fibrosis Foundation

Last reviewed January 2013

See also: Genetic counseling

Down syndrome

Down syndrome is a chromosomal disorder that includes a combination of birth defects. Affected individuals have some degree of intellectual disability, characteristic facial features and, often, heart defects and other health problems. The severity of these problems varies greatly among affected individuals.

How common is Down syndrome?
Down syndrome is one of the most common genetic birth defects. About 1 in 700 (or 6,000) babies are born with Down syndrome each year in the United States. According to the National Down Syndrome Society, there are more than 400,000 individuals with Down syndrome in the United States (2).

What causes Down syndrome?
Down syndrome is caused by extra genetic material from chromosome 21. Chromosomes are the structures in cells that contain the genes.

Each person normally has 23 pairs of chromosomes, or 46 in all. An individual inherits one chromosome per pair from the mother’s egg and one from the father’s sperm. When an egg and sperm join together, they normally form a fertilized egg with 46 chromosomes.

Sometimes something goes wrong before fertilization. A developing egg or sperm cell may divide incorrectly, sometimes causing an egg or sperm cell to have an extra chromosome number 21. When this cell joins with a normal egg or sperm cell, the resulting embryo has 47 chromosomes instead of 46. Down syndrome is called trisomy 21 because affected individuals have three number 21 chromosomes, instead of two. This type of error in cell division causes about 95 percent of the cases of Down syndrome (3).

Occasionally, before fertilization, a part of chromosome 21 breaks off during cell division and becomes attached to another chromosome in the egg or sperm cell. The resulting embryo may have what is called translocation Down syndrome. Affected individuals have two normal copies of chromosome 21, plus extra chromosome 21 material attached to another chromosome. This type of error in cell division causes about 3 to 4 percent of the cases of Down syndrome (3). In some cases, the parent has a rearrangement of chromosome 21, called a balanced translocation, which does not affect his or her health.

About 1 to 2 percent of individuals with Down syndrome have a form called mosaicism (3). In this form, the error in cell division occurs after fertilization. Affected individuals have some cells with an extra chromosome 21 and others with the normal number.

What health problems might a person with Down syndrome have?
The outlook for individuals with Down syndrome is brighter than it once was. Most of the health problems associated with Down syndrome can be treated, and life expectancy is now about 60 years (2). Individuals with Down syndrome are more likely than unaffected individuals to have one or more of the following health conditions:

  • Heart defects: Almost half of babies with Down syndrome have heart defects (3). Some defects are minor and may be treated with medications, while others require surgery. All babies with Down syndrome should be examined by a pediatric cardiologist, a doctor who specializes in heart diseases of children. They also should have an echocardiogram, a special ultrasound of the heart, in the first 2 months of life so that heart defects can be detected and treated, if needed (2, 3).
  • Intestinal defects: About 12 percent of babies with Down syndrome are born with intestinal malformations that require surgery (3).
  • Vision problems: More than 60 percent of children with Down syndrome have vision problems, including crossed eyes (esotropia), near- or far-sightedness and cataracts (3). Glasses, surgery or other treatments usually can improve vision. A child with Down syndrome should be examined by a pediatric ophthalmologist (eye doctor) within the first 6 months of life and have regular vision exams (3).
  • Hearing loss: About 75 percent of children with Down syndrome have some hearing loss (3). Hearing loss may be due to fluid in the middle ear (which may be temporary) and/or defects involving the middle or inner ear (4). Babies with Down syndrome should be screened for hearing loss at birth and again during the first months of life. They also should have regular hearing exams so any problems can be treated before they hinder development of language and other skills (3).
  • Infections: Children with Down syndrome tend to have many colds and ear infections, as well as bronchitis and pneumonia. Children with Down syndrome should receive all the standard childhood immunizations, which help prevent some of these infections.
  • Thyroid problems: About 1 percent of babies with Down syndrome are born with congenital hypothyroidism, a thyroid hormone deficiency that can affect growth and brain development (3). Congenital hypothyroidism can be detected with routine newborn screening tests and treated with oral doses of thyroid hormone. Children with Down syndrome also are at increased risk of acquiring thyroid problems; they should be tested yearly (3).
  • Leukemia: Fewer than 1 in 100 children with Down syndrome develop leukemia (a blood cancer) (3). Affected children often can be successfully treated with chemotherapy.
  • Memory loss: Individuals with Down syndrome are more likely than unaffected individuals to develop Alzheimer’s disease, which is characterized by progressive memory loss, personality changes and other problems. Adults with Down syndrome tend to develop Alzheimer’s disease at an earlier age than unaffected individuals. Studies suggest that about 25 percent of adults with Down syndrome over age 35 have symptoms of Alzheimer’s disease (2).

Some individuals with Down syndrome may have a number of these problems, while others may have none. The severity of these conditions varies greatly.

What does a child with Down syndrome look like?
A child with Down syndrome may have:

  • Eyes that slant upward
  • Small ears that may fold over a little at the top
  • A small mouth, making the tongue appear large
  • A small nose with a flattened nasal bridge
  • A short neck
  • Small hands and feet
  • Low muscle tone
  • Short stature in childhood and adulthood

Most children with Down syndrome have some, but not all, of these features.

How serious is the intellectual disability?
The degree of intellectual disability varies widely. Most affected individuals have intellectual disabilities within the mild to moderate range (2, 3). With proper intervention, few affected individuals have severe intellectual disability (3). There is no way to predict the mental development of a child with Down syndrome based upon physical features.

What can a child with Down syndrome do?
Children with Down syndrome usually can do most things that any young child can do, such as walking, talking, dressing and being toilet-trained. However, they generally start learning these things later than unaffected children.

The exact age that these developmental milestones are achieved cannot be predicted. However, early intervention programs beginning in infancy can help these children achieve their developmental milestones sooner.

Can a child with Down syndrome go to school?
Yes. There are special programs beginning in the preschool years to help children with Down syndrome develop skills as fully as possible. Along with benefiting from early intervention and special education, many children are integrated into the regular classroom. Many affected children learn to read and write, and some graduate from high school and go on to post-secondary programs or college. Many individuals with Down syndrome participate in diverse childhood activities at school and in their neighborhoods.

While there are special work programs designed for adults with Down syndrome, many people with the disorder hold regular jobs. Today, an increasing number of adults with Down syndrome live semi-independently in community group homes where they take care of themselves, participate in household chores, develop friendships, partake in leisure activities and work in their communities.

Can Down syndrome be cured?
There is no cure for Down syndrome. However, some studies suggest that women who have certain versions of some genes that affect how their bodies metabolize (process) the B vitamin folic acid may be at increased risk for having a baby with Down syndrome (5, 6). If confirmed, this finding may provide yet another reason why all women who might become pregnant should take a daily multivitamin containing 400 micrograms of folic acid. Taking folic acid can help reduce the risk of having a baby with certain birth defects of the brain and spinal cord.

Does the risk of Down syndrome increase with the mother’s age?
Yes. The risk of Down syndrome increases with the mother’s age (7):

  • At age 25, the risk of having a baby with Down syndrome is 1 in 1,250.
  • At age 30, the risk is 1 in 1,000.
  • At age 35, the risk is 1 in 400.
  • At age 40, the risk is 1 in 100.
  • At age 45, the risk is 1 in 30.

Even though the risk is greater as the mother’s age increases, about 80 percent of babies with Down syndrome are born to women under age 35. This is because younger women have more babies than older women (1).

What is the risk that parents of a child with Down syndrome will have another affected child?
In general, in each subsequent pregnancy the chance of having another baby with Down syndrome is about 1 in 100 up to age 40. After age 40, the risk is based on the mother’s age (8). If, however, the first child has translocation Down syndrome, the chance of having another child with Down syndrome may be greatly increased.

After birth, the provider takes a blood sample from a baby suspected of having Down syndrome and sends it to a laboratory. The lab does a karyotype (examines the chromosomes) to determine if the baby has Down syndrome and what genetic form of Down syndrome the baby has. This information is important in determining the risk in future pregnancies. The provider may refer parents to a genetic counselor who can explain the results of chromosomal tests in detail, including what the recurrence risks may be in another pregnancy.

Can Down syndrome be diagnosed before the child is born?
Yes. The American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women be offered a screening test for Down syndrome, regardless of the woman’s age. Screening may be a maternal blood test done in the first trimester (at 11 to 13 weeks of pregnancy) along with a special ultrasound to measure the thickness at the back of the baby’s neck (called nuchal translucency). Or it can be a maternal blood test done in the second trimester (at 15 to 20 weeks) without the ultrasound (9). The screening test helps identify pregnancies that are at higher-than-average risk of Down syndrome. However, the screening test cannot diagnose Down syndrome or other birth defects.

Women who have an abnormal screening test result are offered a diagnostic test, such as amniocentesis or chorionic villus sampling (CVS). These tests are highly accurate at diagnosing or, more likely, ruling out Down syndrome.

ACOG also recommends that pregnant women of all ages have the option of bypassing the screening test and choosing a diagnostic test for Down syndrome instead (9). Until recently, only women over age 35 and others considered at increased risk for having a baby with Down syndrome were offered diagnostic testing because amniocentesis and CVS pose a small risk of miscarriage. In the future, screening for Down syndrome may be able to be accomplished with a simple blood test of the pregnant woman that can find and examine minute amounts of fetal genetic material.

Most parents-to-be receive reassuring news from a screening or diagnostic test for Down syndrome. However, if a prenatal diagnostic test shows that the baby has Down syndrome, parents have an opportunity to consider the diagnosis and their options. They also can prepare medically, emotionally and financially for the birth of a child with special needs, such as arranging for delivery in a medically appropriate setting.

Can people with Down syndrome have children?
With rare exceptions, men with Down syndrome cannot father a child (3). A woman with Down syndrome has a 50-50 chance of conceiving a child with Down syndrome, but many affected fetuses are miscarried.

Is the March of Dimes conducting research on Down syndrome?
Yes. Some March of Dimes grantees are investigating why errors in chromosome division occur to be able to prevent Down syndrome and other birth defects caused by abnormalities in the number or structure of chromosomes. Other grantees are investigating the role of specific genes in causing the brain abnormalities and other health problems associated with Down syndrome, with the goal of developing treatments. For example, one grantee is looking at the role of genes in causing a form of leukemia in children with Down syndrome. Another is exploring the role of genes in causing early Alzheimer’s disease in adults with Down syndrome. An international team of scientists has mapped all the genes of chromosome 21. This information eventually may pave the way for treatment of many features of this disorder.

Where can families affected by Down syndrome get additional information?
Many organizations provide information and support for families with children affected by Down syndrome, including:

References

  1. Centers for Disease Control and Prevention (CDC). Down Syndrome. Created 3/11/09.
  2. National Down Syndrome Society. Information Topics. Accessed 4/20/09.
  3. American Academy of Pediatrics Committee on Genetics. Health Supervision for Children with Down Syndrome. Pediatrics, volume 107, number 2, February 2001, pages 442-449 (reaffirmed 9/1/07).
  4. National Institute of Child Health and Human Development (NICHD). Facts About Down Syndrome. Last updated 8/15/08.
  5. O’Leary, V.B., et al. MTRR and MTHFR Polymorphism: Link to Down Syndrome? American Journal of Medical Genetics, January 15, 2002, volume 107, number 2, pages 151-155.
  6. Scala, I., et al. Analysis of Seven Maternal Polymorphisms of Genes Involved in Homocysteine/Folate Metabolism and Risk of Down Syndrome. Genetics in Medicine, volume 8, number 7, July 2006, pages 409-416.
  7. American College of Obstetricians and Gynecologists (ACOG). Your Pregnancy and Birth, 4th Edition. ACOG, Washington, DC, 2005.
  8. Morris, J.K., and Alberman, E. Recurrence of Free Trisomy 21: Analysis of Data from National Down Syndrome Cytogenetic Register. Prenatal Diagnosis, volume 25, number 12, December 2005, pages 1120-1128.
  9. American College of Obstetricians and Gynecologists (ACOG). Screening for Fetal Chromosomal Abnormalities. ACOG Practice Bulletin, number 77, January 2007.

July 2009

Fragile X syndrome

Fragile X syndrome is the most common inherited form of intellectual disability (1, 2). It affects about 1 in 4,000 males and 1 in 6,000 to 8,000 females and occurs in all racial and ethnic groups (1).

What are the signs and symptoms of fragile X syndrome?
Children and adults with fragile X syndrome have a number of mental and physical signs and symptoms ranging from mild to severe. Males tend to be more severely affected than females. Common mental symptoms include (1, 3):

  • Some degree of intellectual disability or learning problems
  • Behavioral problems, such as difficulty paying attention and frequent tantrums
  • Autistic-like behaviors, such as hand flapping and hand biting
  • Delays in learning how to sit, walk and talk
  • Speech problems
  • Anxiety and mood problems
  • Sensitivity to light, sounds, touch and textures

Individuals with fragile X syndrome may have subtle physical signs that tend to become more obvious with age. These may include (1, 3):

  • Large head
  • Long, narrow face
  • Large ears
  • Prominent forehead and chin
  • Overly flexible joints (especially the fingers)
  • In males, enlarged testicles that develop after puberty

Girls with fragile X syndrome generally have fewer physical signs of the condition than males. While most males with fragile X syndrome have intellectual disabilities, only about one-third to one-half of affected females do (3, 4). However, affected girls with normal intelligence may have some of the following symptoms (5):

  • Learning disabilities involving math
  • Attention difficulties
  • Speech delays
  • Emotional problems, such as anxiety, depression and shyness
  • Poor social skills

Do children with fragile X syndrome have medical problems?
Most children with fragile X syndrome do not have serious medical problems and generally have a normal life span. However, about 15 percent of affected boys and about 5 percent of girls develop seizures, which often can be controlled with medication (5). Children with fragile X syndrome may be at increased risk for chronic inner ear infections and may need to have tubes placed in their ears (5).

Children with fragile X syndrome may have heart murmurs that often are caused by a condition called mitral valve prolapse (5). This condition usually is not life-threatening and, in most cases, does not require treatment.

What causes fragile X syndrome?
Fragile X syndrome is caused by an abnormality in a single gene. In 1991, a researcher supported by the March of Dimes discovered that fragile X syndrome is caused by a mutation (change) in a gene called FMR-1 located on the X chromosome (6).

Each person has 23 pairs of chromosomes, or 46 individual chromosomes. The pair of sex chromosomes (X and Y) determines whether a person is male or female. Normally, females have two X chromosomes, and males have one X chromosome and one Y chromosome. Because females have two X chromosomes, a female who inherits one X chromosome with the abnormal FMR-1 gene still has the other unaffected X chromosome. Therefore, females are affected by fragile X syndrome less frequently than males. When affected, females tend to have less severe symptoms than males. Males generally are more severely affected because they have only one X chromosome, and it contains the abnormal gene.

The mutation that causes fragile X syndrome is a genetic “stutter.” This means that a small section of genetic material within the gene is repeated too many times. Most people who do not have fragile X syndrome have between 5 and 40 repeats of this section of the gene. People who have more than 200 repeats of the gene have fragile X syndrome. More than 200 repeats is called a full mutation. A full mutation causes the gene to turn off and not make the protein it usually makes. The protein normally is found in many types of cells but mostly in nerve cells (3). Scientists think the protein helps brain development and may help nerve cells in the brain communicate (3, 5).

Fragile X syndrome gets its name from the appearance of the section of the X chromosome where the gene mutation occurs. In certain conditions under a microscope, the section of the chromosome looks fragile, as if it is dangling by a thread.

How is fragile X syndrome diagnosed?
Fragile X syndrome is diagnosed with a blood test. A blood sample is sent to a laboratory where it is checked for the gene mutation. The test is available at most major medical centers. A health care provider, genetic counselor or the National Fragile X Foundation can provide information on testing locations.

Boys with fragile X syndrome usually are diagnosed at about 3 years of age (often at about 35 to 37 months) (7). Girls have milder symptoms and usually are diagnosed a little later (often at about 41 months) (7).

How is fragile X syndrome inherited?
Inheritance of fragile X syndrome is complicated. Individuals with a family history of this disorder should consult a genetic counselor to learn more about the risks of passing the disorder to their children.

  • Normal number of repeats: Individuals with a normal number of repeats (5 to 40) cannot pass fragile X syndrome to their offspring. The number of repeats generally does not change when passed from parent to child.
  • Intermediate number of repeats: When a person has 41 to 58 repeats (called the gray zone), the number of repeats can sometimes increase slightly when passed from parent to child. These parents are not at risk of having a child with fragile X syndrome. However, the number of repeats can grow with each generation, so their grandchildren could be at risk.
  • Premutation: Individuals with 59 to 200 repeats have a premutation (3). Both men and women can be carriers of a premutation. About 1 in 250 women and 1 in 800 men carries a premutation (8). However, only women who carry a premutation are at risk for having a child with fragile X syndrome.

    A mother with a premutation has a 50-percent chance of passing the abnormal gene to her baby in each pregnancy. Some children who inherit the abnormal gene have a premutation and no symptoms of fragile X syndrome. However, the number of repeats is likely to expand when the gene is passed from mother to child. So the number of repeats can increase from a premutation to a full mutation (more than 200 repeats). Children with a full mutation have fragile X syndrome.
    A father with a premutation passes it to all of his daughters but to none of his sons. Daughters generally have no symptoms of fragile X syndrome, but they are carriers of a premutation that they can pass on to their own children. Fathers with a premutation do not pass it to their sons because males do not get an X chromosome from their father.
  • Full mutation: Individuals with more than 200 repeats have a full mutation. A woman with a full mutation has a 50-percent chance of passing it to her baby in each pregnancy. Men with a full mutation generally do not reproduce.

Do individuals with a premutation have health risks?
Individuals with a premutation do not have fragile X syndrome. However, they may be at increased risk of:

  • Learning and behavioral problems: Individuals with a premutation generally have normal intelligence. However, some may develop subtle behavior or learning problems (1, 3, 5).
  • Fragile X-associated tremor/ataxia syndrome: At least 30 percent of males over age 50 with a premutation develop a neurologic (nervous system) disease that causes tremors (shaking) and uncoordinated muscle movement (1). Between 4 and 8 percent of women with the premutation may develop this disorder, though they tend to be older than affected men and have milder symptoms (5).
  • Premature ovarian failure: About 20 percent of women with a premutation develop premature (early) ovarian failure and early menopause, which means they happen before age 40. This can affect a woman’s fertility (1, 2).

Individuals with a full mutation generally do not develop neurologic disease or premature ovarian failure and early menopause.

When is fragile X testing recommended for children?
A health care provider may recommend testing a child for fragile X syndrome if the child has intellectual disabilities, developmental delay or autism. Testing is especially important if the child also has (9):

  • Physical or behavioral signs and symptoms of fragile X syndrome
  • A family history of fragile X syndrome or intellectual disabilities of unknown cause

When is fragile X testing recommended for women planning pregnancy?
Women who are planning pregnancy may be offered carrier screening for fragile X syndrome if they have:

  • A family history of fragile X syndrome or a disorder related to fragile X syndrome
  • A family history of intellectual disabilities with no known cause
  • A personal or family history of developmental delay or autism
  • A personal history of reproductive or fertility problems that could be related to early ovarian failure

Women and their partners who are found to be carriers of a fragile X mutation or premutation should talk to a genetic counselor. These health professionals help families understand the chances of a birth defect occurring in a pregnancy and can discuss the possibility of prenatal testing. Genetic counseling is available at most large medical centers and teaching hospitals. To find a genetic counselor, individuals can ask their health care provider or contact the National Society of Genetic Counselors.

Can fragile X syndrome be diagnosed before birth?
Prenatal tests (amniocentesis and chorionic villus sampling [CVS]) can determine whether the baby of a carrier mother has inherited a full mutation or premutation. Occasionally, CVS cannot determine whether the baby has a large premutation or a full mutation. In these cases, providers may recommend follow-up with amniocentesis

How is fragile X syndrome treated?
There is no cure for fragile X syndrome. However, an individualized treatment plan, beginning in the preschool years, can help affected children reach their full potential. Most children with fragile X syndrome can benefit from treatment by a team of health professionals and special educators. The team may include speech/language therapists, physical and occupational therapists, special educators, psychologists and pediatricians.

Some children with fragile X syndrome benefit from medications that improve their behavioral symptoms so they are better able to learn. Some commonly used medications include:

  • Antidepressants, used for anxiety and mood problems
  • Stimulants (such as Ritalin), used for hyperactivity and attention problems
  • Antiseizure drugs, used for behavior and mood problems
  • Antipsychotics, used for aggression and mood problems

Researchers are developing and testing drugs that may help correct the abnormal brain-cell connections that contribute to many of the intellectual and behavioral features of fragile X syndrome. One study suggested that individuals treated with one of these drugs (called fenobam) showed calmed behavior, with less anxiety and hyperactivity (10). Though these results are promising, more studies are needed on the safety and effectiveness of fenobam and related drugs.

Does the March of Dimes support research on fragile X syndrome?
March of Dimes research grantees are investigating how loss of the protein made by the fragile X gene may interfere with communication between nerve cells in the brain, in order to develop effective treatments. Another is studying how the gene mutation contributes to autistic-like behaviors, in order to improve the diagnosis and treatment of both fragile X syndrome and autism. One grantee is examining language development in girls with fragile X syndrome, in order to improve diagnosis and treatment of affected girls.

Where can a family get additional information on fragile X syndrome?

References

  1. Centers for Disease Control and Prevention (CDC). (2006). Fragile X Syndrome. Retrieved November 9, 2009.
  2. American College of Obstetricians and Gynecologists (ACOG). (2006). ACOG Committee Opinion number 338: Screening for fragile X syndrome. Washington, D.C.: Author.
  3. Saul, R.A. & Tarleton, J.C. (2008). FMR1-Related Disorders. Gene Reviews. Retrieved November 9, 2009.
  4. Fragile X Research Foundation. (2009). About Fragile X. Retrieved November 6, 2009.
  5. Hagerman, R.J., Berry-Kravis, E., Kaufman, W.E., Ono, M.Y., Tartaglia, N. et al. (2009). Advances in the treatment of fragile X syndrome. Pediatrics, 123 (1), 378-390.
  6. Verkerk. A.J.M.H., Pieretti, M., Sutcliffe, J.S., Fu, Y-H., Kuhl, D.P.A., et al. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65, 905-914.
  7. Bailey, D.B., Raspa, M., Bishop, E. & Holiday, D. (2009). No change in the age of diagnosis for fragile X syndrome: Findings from a national parent survey. Pediatrics, 124 (2), 527-533.
  8. McConkie-Rosell, A., Abrams, L., Finucane, B., Cronister, A., Gane, L.W., et al. (2007). Recommendations from multi-disciplinary focus groups on cascade testing and genetic counseling for fragile X-associated disorders. Journal of Genetic Counseling, 16 (5), 593-606.
  9. Sherman, S., Pletcher, B.A. & Driscoll, D.A. (2005). American College of Medical Genetics Practice Guideline: Fragile X syndrome: diagnostic and carrier testing. Genetics in Medicine, 7 (8), 584-587.
  10. Berry-Kravis, E.M., Hessl, D., Coffey, S., Hervey, C., Schneider, A., et al. (2009). A pilot open-label single-dose trial for fenobam in adults with fragile X syndrome. Journal of Medical Genetics, 46, 266-271.

April 2010

Genital and urinary tract defects

Genital and urinary tract defects are birth defects. Birth defects are health conditions that are present at birth that change the shape or function of one or more parts of the body. They can cause problems in overall health, how the body develops, or in how the body works.

Genitals are sex organs. Some genitals, like the penis, are outside the body. Others, like the ovaries, are inside the body. The urinary tract is the system of organs (like the kidneys and bladder) that helps your body get rid of waste and extra fluids.

What problems can genital and urinary tract defects cause?
Genital and urinary tract defects affect one or more of a baby’s body parts, including: 

  • Kidneys, the pair of organs that remove waste from the blood and make urine
  • Bladder, the sac that holds urine
  • Ureters, two tubes that carry urine from the kidneys to the bladder
  • Urethra, the tube that carries urine out of the body from the bladder
  • Male genitals, including the penis and testicles. Testicles (also called testes) are two egg-shaped organs usually found in the sac (called the scrotum) behind the penis. They make sperm and testosterone (a male hormone).In some boys, the testes are inside the belly instead of the scrotum; this condition is called undescended testes.
  • Female genitals, including the vagina, ovaries and uterus (womb)

Genital and urinary tract defects can cause:

  • Urinary tract infections (UTIs)
  • Pain
  • Kidney damage
  • Kidney failure. This is a serious condition that happens when the kidneys don’t work well and allow waste to build up in the body.

What causes genital and urinary tract defects?
We don’t know the exact cause of most of these conditions. But some happen when parents who have the condition, or carry the gene for the condition, pass it to their children. Genes are a part of your body’s cells that stores instructions for the way your body grows and works.

If you already have a child with a genital or urinary tract defect and are thinking about having another baby, you may want to speak with a genetic counselor. This is a person who is trained to help you understand about how genes, birth defects and other medical conditions run in families, and how they can affect your health and your baby's health.

How do you know if your baby has one of these conditions?
Many urinary tract defects can be diagnosed before birth with an ultrasound. Ultrasound uses sound waves and a computer screen to make a picture of a baby in the womb. After birth, genital defects often are diagnosed during your baby’s checkup in the hospital nursery.

Your baby gets tested for a condition called congenital adrenal hyperplasia (also called CAH) as part of newborn screening after birth. Newborn screening checks for serious but rare and mostly treatable conditions. It includes blood, hearing and heart screening.

What are some common genital and urinary tract defects and how are they treated?
Common genital and urinary tract defects include:

Ambiguous genitals. In this condition, a baby’s genitals outside the body, like the penis or vagina, aren’t obviously either male or female. About 1 in 4,500 babies (less than 1 percent) has ambiguous genitals.

Ambiguous genitals are a common sign of several disorders of sexual development (also called DSDs). These are conditions in which a baby’s genitals outside the body are different from what a baby’s chromosomes (XX for females, XY for males) or organs inside the body say they should be. Treatment for these conditions may include hormone treatment or surgery on the genitals.

Bladder exstrophy and epispadias. Bladder exstrophy is when the bladder is turned inside out and bulges outside of the belly. It can involve other parts of the body, including the urinary tract, muscles, bones and the digestive system. This condition affects about 1 in 30,000 babies (less than 1 percent). It happens in boys slightly more often than girls.

Epispadias is a defect in the urethra that often happens with bladder exstrophy. It can cause these problems:

  • For boys, a shorter-than-normal urethra with an opening on the upper part of the penis instead of the penis tip
  • For boys, a penis that looks short and flat and may curve upward
  • For girls, a clitoris that’s split and, sometimes, the urinary opening in the wrong place. The clitoris is a female external sex organ.
  • For boys and girls, bladder control problems

Some babies need surgery to help treat problems with bladder control and how the genitals look and work.

Hydronephrosis. In this condition, one or both kidneys swell because a blockage in the urinary tract causes urine to back up into the kidneys. It affects up to 1 in 100 (1 percent) pregnancies.

When hydronephrosis happens to your baby in the womb, it’s called fetal hydronephrosis. It usually goes away without lasting problems. But sometimes the blockage can damage the developing kidneys or become life-threatening for your baby. If hydronephrosis is diagnosed before birth with ultrasound, your provider checks your baby with repeat ultrasounds to see if it goes away or gets worse.

Most babies don’t need treatment until after birth. But if hydronephrosis becomes life-threatening before birth, you may need to give birth early or have surgery to put a shunt (small tube) into your baby’s bladder while still in the womb. The shunt drains urine into the amniotic fluid until birth. After birth, mild hydronephrosis may go away without treatment. If the blockage doesn’t go away, your baby may need surgery.

Hypospadias. This condition affects only boys. It’s when the opening of the urethra is on the underside of the penis instead of at the tip of the penis. Hyposadias affects at least 1 in 300 baby boys (less than 1 percent).

Boys with this condition may have a curved penis. This may cause them to have problems with spraying urine, so they may need to sit down to urinate. And in some boys, the testicles don’t fully drop down into the scrotum before birth. Without treatment, hyposadias can lead to problems with sex or urinating later in life.

Hypospadias usually is diagnosed in baby boys during a physical exam after birth. Most babies need surgery to correct the condition. If you plan to have your son circumcised, you may need to wait because your baby’s provider may use the penis foreskin in surgery to help fix hypospadias. Circumcision is a surgical procedure that removes foreskin from the penis. Foreskin is the fold of skin that covers the tip of the penis.

Kidney dysplasia (also called renal dysplasia or multicystic dysplastic kidney). In this condition, cysts grow inside of one or both kidneys. The cysts may appear to actually replace one or both kidneys. A blockage in a baby’s urinary tract early in pregnancy may cause kidney dysplasia. It affects about 1 in 2,000 babies (less than 1 percent).

Kidney dysplasia usually happens in only one kidney. In these cases, babies have few, if any, health problems. But if it affects both kidneys, babies may not survive pregnancy. Babies who do survive need dialysis and a kidney transplant very soon after birth.

Kidney dysplasia is often found during an ultrasound. After birth, it may be found during an exam for a urinary tract infection or other medical condition.

Polycystic kidney disease (also called PKD). This condition causes cysts (fluid-filled sacs) to grow in the kidneys. The cysts make the kidneys work poorly, leading to kidney failure. Cysts also may develop in other organs, like the liver. There are two major forms of PKD:

  1. Autosomal dominant PKD is the more common form. It usually happens when a baby inherits the PKD gene change from a parent. A gene change (also called a mutation) is a change to instructions that are stored in a gene. The change sometimes can cause birth defects and other health conditions. But 1 in 10 (10 percent) people with autosomal dominant PKD don’t have a family history of PKD. Symptoms usually appear in adulthood, but some children have symptoms. This type of PKD affects between 1 in 500 and 1 in 1,000 people (less than 1 percent).
  2. Autosomal recessive PKD is rare and happens when both parents (who aren’t affected by PKD themselves) pass the PKD gene change to their child. Cysts may develop before birth and can be life-threatening. Symptoms also can appear later in childhood. Up to 1 in 20,000 babies (less than 1 percent) is born with this form of PKD.

PKD treatments include:

  • Blood pressure medicines, diuretics (medicine that helps your body get rid of salt and water) and a low-salt meal plan
  • Antibiotics to treat urinary tract infections. Antibiotics are medicines that kill infections caused by bacteria.
  • Draining cysts that are painful, infected, bleeding or causing a blockage
  • Dialysis. This treatment filters your blood to rid your body of harmful wastes, extra salt and water.
  • Surgery to remove one or both kidneys. If both kidneys are removed, you need dialysis or a kidney transplant. This is surgery to place a healthy kidney into a person with kidney failure.

Renal agenesis. There are two kinds of renal agenesis:

  1. Unilateral renal agenesis is when a baby is born with just one kidney instead of two. Most babies with this condition grow and develop normally. But some have other urinary tract defects that may cause problems for the one kidney. Providers can use ultrasound and other tests to check for problems that need special care. Between 1 in 450 and 1 in 1,000 babies (less than 1 percent) is born with this condition.
  2. Bilateral renal agenesis is when a baby is born without kidneys. Babies with this condition may not survive and often die in the first days of life. They need dialysis to survive. About 1 in 3,000 babies (less than 1 percent) is born with this condition.

Last reviewed February 2013

See also: Birth defects, Genetic counseling

Hearing impairment

Hearing impairment is the decreased ability to hear and discriminate among sounds. It is one of the most common birth defects. Each year in the United States, about 12,000 babies (3 in 1,000) are born with some degree of hearing impairment (1). Hearing impairment that is present at birth is called congenital hearing impairment. Hearing impairment also can develop later in childhood or during adulthood.

The Centers for Disease Control and Prevention (CDC) recommends that all babies be screened for hearing impairment before 1 month of age, preferably before they leave the hospital after birth (1). This is because language and communication develop rapidly during the first 2 to 3 years of life, and undetected hearing impairment can lead to delays in developing these skills. Without newborn screening, children with hearing impairment often are not diagnosed until 2 to 3 years of age (1).

The goal of early screening, diagnosis and treatment is to help children with hearing impairment develop language and academic skills equal to those of their peers. Most states have an Early Hearing Detection and Intervention Program to help ensure that all babies are screened, and that infants who do not pass the screening receive the follow-up care they need. The March of Dimes, the American Academy of Pediatrics (AAP), the CDC and others strongly support these programs.

What causes hearing impairment in babies and children?
Hearing impairment can be genetic (inherited) or non-genetic. Non-genetic causes include illness or injury before, during or after birth. In some cases, the cause of hearing impairment is not known. About 90 percent of babies with congenital hearing impairment are born to parents with normal hearing (1, 2).

Genetic factors are believed to cause 50 percent of cases of hearing impairment in infants and young children (1). Scientists believe that mutations (changes) in as many as 400 genes may contribute to hearing impairment (1, 3).

Genetic causes of hearing impairment can be:

  • Syndromatic: Syndromatic means that the hearing impairment happens with a specific group of birth defects. It’s not the only birth defect a baby has. This type of hearing impairment accounts for about 30 percent of genetic cases (1, 3).
  • Non-syndromatic: Non-syndromatic means that hearing impairment is the only birth defect a baby has. About 50 percent of cases of non-syndromatic genetic hearing impairment are caused by a mutation in a gene called connexin 26 (3).

About 25 percent of cases of hearing impairment are caused by non-genetic factors (1). These include premature birth (before 37 completed weeks of pregnancy) and illnesses during pregnancy, such as:

Non-genetic causes of hearing impairment after birth include:

  • Head injuries
  • Childhood infections (such as meningitis, measles or chickenpox)
  • Certain medications (such as the antibiotic streptomycin and related drugs)
  • Ear infections (otitis media) – These usually cause temporary hearing impairment. However, frequent and poorly treated ear infections can cause permanent hearing impairment.

The causes of the remaining 25 percent of cases of hearing impairment in infants and children are unknown (1).

Are there different types of hearing impairment?
Yes. When sound enters the outer ear (called either auricle or pinna), it moves through the ear canal to the eardrum (tympanic membrane). Incoming sound causes the eardrum to vibrate, which moves three small bones (ossicles) in the middle ear. In this way, the ear canal, the eardrum and the middle ear transmit sound from the outside to the inner ear (cochlea). Within the inner ear, thousands of tiny hair cells detect the incoming vibrations and convert them into signals that are relayed to the auditory nerves, which send neural impulses to the hearing center in the brain.

Hearing impairment can occur in different parts of the hearing pathway.

  • Conductive hearing impairment occurs when something interferes with sound passing through the outer or middle ear. A blockage in the ear canal, damage to the eardrum, and fluid or an infection in the middle ear (otitis media) are examples of conditions that can cause conductive hearing impairment. This type of hearing impairment usually is temporary and often can be corrected with medication or draining fluid out of the ear.
  • Sensorineural hearing impairment occurs when the hair cells in the inner ear cannot detect all incoming vibrations or when neural impulses are not transmitted to the brain. Prenatal infections or genetic factors can cause this type of hearing impairment. Sensorineural hearing impairment generally is permanent. However, many children can be helped with hearing aids that amplify sound. Sensorineural hearing impairment also can result from damage to the brain’s hearing center.
  • Mixed hearing impairment occurs when a child has both a conductive impairment and a sensorineural impairment. Early and proper treatment of acute ear infections is crucial to protecting children from additional hearing impairment.

How are newborns screened for hearing impairment?
Newborns are screened for hearing impairment with one of two tests. Both tests measure how a baby responds to sound. The tests take 5 to 10 minutes, are painless and can be done when the baby is sleeping.

Otoacoustic emissions (OAE) test: A small microphone is placed in the baby’s ear. The microphone, connected to a computer, sends soft clicking sounds or tones into the ear and records the inner ear’s response to sound.
Automated auditory brainstem response (AABR) test: Soft clicking sounds are presented to the ear through small earphones. Sensors placed on the head and connected to a computer measure brain wave activity in response to sound.

What happens if a baby does not pass the hearing screening?
If a baby does not pass the OAE or the AABR:

  • The test should be repeated or
  • The baby should be referred to a hearing specialist (audiologist) or an ear, nose and throat (ENT) specialist (otolaryngologist). The specialist does more extensive tests (diagnostic tests) to determine if the baby has a hearing impairment.

It is important for babies who don’t pass the screening to be assessed by specialists who have experience testing very young children. Diagnostic testing should be completed by the time a baby is 3 months of age (1, 4).

Screening tests cannot diagnose hearing impairment; they only indicate that there may be a problem. Up to 10 percent of babies have abnormal results on their hearing screening test (1). Diagnostic tests show that most of these babies do not have hearing impairment.

What tests are used to diagnose hearing impairment?
The most common diagnostic hearing test for infants under 6 months of age is the diagnostic auditory brainstem response test (2). It is similar to the AABR, but it provides more information and must be given by a specialist.

Tests used to diagnose hearing impairment in older infants and children include (2):

  • Visual reinforcement audiometry (VRA): This test is used in children between 6 months and 2½ years of age. In VRA testing, a series of sounds are presented to the child through earphones or speakers. The child is asked to turn toward any sound and is rewarded with an entertaining visual image for responding.
  • Conditioned play audiometry (CPA): In CPA, children between 2½ and 4 years of age are asked to perform a simple play activity (like placing a ring on a peg) when they hear a sound.
  • Conventional audiometry: Children ages 4 years and older are asked to press a button or raise their hand when they hear a sound.

The AAP recommends that children with a risk factor for hearing impairment have one of these diagnostic tests by 2 to 2½ years of age, even if they pass the newborn screening test (2).

What are some risk factors for hearing impairment?
Children who have one of these risk factors should have a diagnostic hearing test (2):

  • The parent suspects that the child is not responding normally to sounds.
  • The child has had persistent ear infections, meningitis or other illness that can cause hearing impairment.
  • The child was infected before birth with cytomegalovirus or certain other infections.
  • The child has been diagnosed with a syndrome that can include hearing impairment.
  • The child has certain craniofacial (defects of skull and face) abnormalities, including ear abnormalities.
  • There is a family history of permanent childhood hearing impairment.
  • The child was treated in the NICU (newborn intensive care unit) for more than 5 days or was treated with certain medications.
  • The child suffered a head injury.

What are some signs of hearing impairment in infants and young children?
Parents should be alert to any signs of hearing impairment and discuss them with their child’s health care provider. Some signs include:

  • Failure to startle at loud sounds
  • Not turning toward the sound of a voice or imitating sounds after about 6 months of age
  • Lack of babbling by 12 months of age
  • Failure to respond to name by 12 months of age
  • Not using single words by 18 months of age
  • Failure to follow simple directions by 18 months of age

Parents should be concerned about hearing impairment in older children if they:

  • Develop vocabulary more slowly than their peers
  • Have speech that is difficult to understand or that is too loud or too soft
  • Often ask for words to be repeated
  • Turn on the TV too loud
  • Appear inattentive at school and have trouble learning to read or perform simple mathematics.

How is hearing impairment treated?
A child with congenital hearing impairment should begin receiving treatment before 6 months of age (1). Studies suggest that children treated this early usually are able to develop communication skills (using spoken or sign language) that are as good as those of hearing peers (4).

Because of the Individuals with Disabilities Education Act, children with a hearing impairment between birth and 3 years of age have the right to receive early intervention services at little or no cost. The public school system provides early intervention and special education programs for children after age 3.

A number of treatment options are available, and parents need to decide which are most appropriate for their child. They should consider the child’s age, developmental level and personality, and the severity of the hearing impairment. Ideally, a team of experts, including the child’s health care provider, an otolaryngologist, a speech-language specialist, an audiologist and one of the child’s teachers, work closely with the parents to create an individualized family service plan. This treatment plan can be changed as the child gets older.

Children as young as 4 weeks of age can benefit from a hearing aid (4). These devices amplify sound, making it possible for many children to hear spoken words and develop language. However, hearing aids help some children with hearing impairment more than others. Some children with severe to profound hearing impairment may not be able to hear enough sound, even with a hearing aid, to be able to hear speech. Providers often recommend a behind-the-ear hearing aid for young children because it is safer and more easily fitted and adjusted as the child grows, as compared to one that fits inside the ear.

Parents also need to decide how their family and child are going to communicate. If the child is going to communicate with speech, she may need help with listening and lip-reading skills. Many children with hearing impairment also need some type of speech or language therapy.

A child also can learn to communicate using a sign language. A widely used type of sign language is American Sign Language (ASL), which has rules and grammar that are distinct from English. There also are several variations of sign language that can be used along with spoken English.

When is surgery recommended?
Health care providers may recommend surgery if a child has a permanent conductive hearing impairment caused by malformations of the outer or middle ear, or by repeated ear infections. Although fluid in the middle ear usually causes temporary hearing loss, chronic (long-lasting or frequent) ear infection can cause a child to fall behind in language skills. In some cases, a provider may suggest inserting a tube through the eardrum to allow the middle ear to drain. This procedure generally does not require an overnight hospital stay.

What is a cochlear implant?
Surgery may be an option for some children with severe to profound sensorineural hearing loss. A device called a cochlear implant can be surgically inserted in children as young as 12 months of age to stimulate hearing (5). One part of the device sits behind the ear. The second part is surgically placed under the skin and inside the skull, with wires threaded into the inner ear. The surgery sometimes requires an overnight hospital stay. With language and speech therapy, children with cochlear implants may learn to understand speech and speak reasonably well, but the amount of improvement is variable.

A 2003 study found that bacterial meningitis, although rare, occurred more often in children with cochlear implants than in other children of the same age (6). Parents of children with cochlear implants should be aware of the symptoms of meningitis (high fever, headache, stiff neck, nausea, discomfort looking into bright lights, sleepiness and confusion) and report them to the child’s health care provider immediately (1). Parents should also make sure their child’s vaccinations are up to date, including the pneumococcal and haemophilus vaccines that help protect against meningitis.

What other conditions are common in children with hearing impairment?
At least one-third of children with hearing impairment have other conditions, including vision problems, learning disabilities, attention problems and autism (2). The child’s health care provider usually screens for these conditions during regular well-child visits. However, parents should always discuss any concerns about their child’s development with his health care provider.

Does the March of Dimes support research on hearing impairment?
March of Dimes grantees are exploring the role that specific genes play in causing hearing impairment, with the ultimate goal of developing new treatments for genetic hearing impairment. Several grantees are seeking to prevent hearing impairment by preventing prenatal infections (such as cytomegalovirus and toxoplasmosis) that can cause it. Others are seeking to improve diagnosis and treatment of individuals with hearing impairment. One is evaluating deaf children’s difficulty learning to spell and read in order to develop improved education programs. Another is seeking to increase the accuracy and efficiency of diagnosing hearing impairment during the first year of life.

For more information

References

  1. Centers for Disease Control and Prevention (CDC). (2009). Early Hearing Detection & Intervention Program. Retrieved October 1, 2009.
  2. American Academy of Pediatrics (AAP). (2009). Clinical Report–Hearing Assessment in Infants and Children: Recommendations Beyond Neonatal Screening. Pediatrics, 124(4), 1252-1263.
  3. Smith, R. & Van Camp, G. (2008). Deafness and Hereditary Hearing Loss Overview. GeneReviews. Retrieved October 1, 2009.
  4. American Speech-Language-Hearing Association. (2009). Children and Hearing Aids. Retrieved October 2, 2009.
  5. National Institute on Deafness and Other Communication Disorders. (2009). Cochlear Implants. Retrieved October 1, 2009.
  6. Reefhuis, J., Honein, M.A., Whitney, C.G., Chamany, S., Mann, E.A., et al. (2003). Risk of Bacterial Meningitis in Children with Cochlear Implants. New England Journal of Medicine, 349(5), 435-445.

March 2010

Marfan syndrome

Marfan syndrome is a genetic disorder that affects connective tissue. Connective tissue holds other tissues together. Because connective tissue is found throughout the body, Marfan syndrome can affect many body systems, including the heart, blood vessels, bones, eyes, lungs and skin. It does not affect intelligence. Signs and symptoms of Marfan syndrome can be mild or severe. They may be present at birth or become apparent in childhood or in adult life.

How common is Marfan syndrome?
Marfan syndrome affects more than 200,000 Americans (about 1 in 5,000 to 1 in 10,000) (1, 2). The disorder affects males and females of all races and ethnic groups. The condition is named for Dr. Antoine Marfan who, in 1896, described a 5-year-old girl with unusually long, slender fingers and limbs and other skeletal abnormalities.

How are individuals with Marfan syndrome affected?
Many affected individuals are tall, slender and loose-jointed. Arms, legs, fingers and toes often are unusually long. Some people with Marfan syndrome have low foot arches (flat feet), and others have high arches. Individuals with Marfan syndrome usually have long, narrow faces, and their teeth are generally crowded.

Individuals with Marfan syndrome can have one or more of the problems described below. The severity of the effects of Marfan syndrome varies greatly, even within the same family.

  • Heart and blood vessel problems: The most serious problem associated with Marfan syndrome is weakness of the wall of the aorta. The aorta is the body’s largest artery, which carries oxygen-rich blood from the left side of the heart to the rest of the body.
    In Marfan syndrome, the wall of the aorta gradually weakens and stretches (aortic dilation). Eventually, this can cause a tear (dissection) in the lining of the aorta. Blood can leak out through the tear into the aortic wall, sometimes causing a rupture that allows blood to leak into the chest or abdomen. If not detected and treated, these complications can cause sudden death.
  • Abnormal heart valves: Heart valves are tiny flaps or gates that keep the blood flowing in one direction through the heart. With Marfan syndrome, the heart’s mitral valve tends to be large and floppy (mitral valve prolapse). An abnormal mitral valve can allow blood to briefly flow backwards during a heartbeat. Sometimes this creates an abnormal sound (heart murmur) that a health care provider may hear through a stethoscope. Mitral valve prolapse can sometimes be associated with irregular or rapid heartbeat and shortness of breath.
  • Skeletal abnormalities: Many affected individuals have a lateral (sideways) curve of the spine called scoliosis. Sometimes there is a sharp, forward curvature called kyphosis. Many individuals have a breastbone that protrudes outward (called pectus carinatum) or sinks inward (called pectus excavatum). These chest abnormalities can sometimes affect heart or lung function.
    Sometimes the connective tissue that surrounds the spinal cord loosens and stretches out. This condition is called dural ectasia and can cause pain in the lower back or legs and numbness or weakness in the legs.
  • Lung problems: Persons with Marfan syndrome sometimes develop breathing problems, such as shortness of breath. Breathing problems may result from skeletal abnormalities that do not allow the chest to fully expand or from sudden collapse of the lungs (called spontaneous pneumothorax).
    Adults with Marfan syndrome are at increased risk for early emphysema, a breathing disorder usually associated with smoking, even if they don’t smoke. Individuals with Marfan syndrome also may have short pauses in breathing during sleep, called sleep apnea.
  • Eye problems: The lens of one or both eyes is off-center in more than 60 percent of persons with Marfan syndrome (1, 3). This is called ectopia lentis. Most affected individuals are nearsighted and have astigmatism (the eyes cannot focus clearly).

    Individuals with Marfan syndrome are at increased risk for detachment of the retina (tears in the light-sensing lining at the back of the eye), cataracts (clouding of the lens of the eye) and glaucoma (increased pressure in the eye). Individuals with Marfan syndrome often develop cataracts and glaucoma at an earlier age than individuals in the general population. Retinal detachment and glaucoma can lead to vision loss.

How is Marfan syndrome diagnosed?
An evaluation for Marfan syndrome generally includes:

  • A complete physical examination.
  • An eye examination by an ophthalmologist (eye doctor). The ophthalmologist uses eye drops to fully dilate the pupils of the eyes and examines them with a slit-lamp (a microscope with a light attached) to look for lens dislocation.
  • Heart tests, including an electrocardiogram (EKG) and an echocardiogram. An EKG measures electrical activity in the heart. An echocardiogram is a noninvasive ultrasound that lets doctors look for involvement of the heart and blood vessels. Imaging tests, such as a computed tomography (CT scan) or magnetic resonance imaging (MRI), may be used to check the condition of the aorta.
  • A family history to determine if there are other family members known or suspected to have Marfan syndrome and/or who died early due to an unexplained heart disorder or an aneurysm. An aneurysm is a bulging of a blood vessel, such as the aorta, that sometimes can cause the vessel to rupture.
  • Genetic testing of a blood sample to help confirm the diagnosis.
  • An MRI of the lower spine to look for dural ectasia.

How is Marfan syndrome treated?
Advances in treatment have greatly improved the outlook for children and adults with Marfan syndrome. Today, the life expectancy of individuals with the disorder who receive proper treatment is about 70 years (1, 2).

Most of the problems associated with Marfan syndrome can be managed effectively, as long as they are diagnosed early. The disorder usually is treated by a team of experienced physicians and health care professionals, overseen by a single doctor who knows all of its aspects.

The team of physicians should include a cardiologist (heart doctor). Affected individuals need to have a series of echocardiograms (called serial echocardiograms) to measure the dimensions of the aorta and check the condition of the heart valves. These and other tests help the doctors determine whether or not treatment is needed and when intervention should take place.

How are heart problems treated?
To help prevent or reduce heart problems, doctors often recommend treatment with high blood pressure medications called beta blockers. These medications reduce the strength and frequency of heartbeats, reducing stress on the wall of the aorta. Studies suggest that beta blockers may slow down the rate of dilation of the aorta and help prevent it from tearing (2, 4). Individuals who cannot tolerate beta blockers are sometimes treated with other high blood pressure medications, such as calcium channel blockers or angiotensin-converting enzyme inhibitors (4).

New studies suggest that high blood pressure medications called angiotensin-receptor blockers may help prevent or even reverse aortic dilation (5, 6). Larger studies are underway to test the effectiveness of these drugs.

In spite of the use of medication, the aorta sometimes continues to dilate. Doctors recommend surgery to repair the aorta before there is a danger of it tearing or dissecting. Doctors evaluate a number of factors when considering surgery and planning its timing. These factors include the size of the aorta and the rate at which it is dilating, family history of aortic dilation/dissection, and whether the aortic valve is leaking.

There are a few surgical options for repairing the aorta. In one operation, the surgeon replaces a section of the aorta with a synthetic tube (called a composite graft) and sometimes repairs or replaces the aortic valve. More recently, some individuals with Marfan syndrome have had a valve-sparing procedure in which the aortic valve is retained and a portion of the aorta closest to the heart is replaced.

Individuals with Marfan syndrome should have aortic surgery performed at a hospital where the surgeons are experienced with Marfan syndrome. Affected individuals should discuss the pros and cons of various surgical options with their surgeon.

Early preventive surgery for aortic dilation is safer than waiting until emergency surgery is needed. A 1999 study showed that with preventive surgery, the death rate was 1.5 percent vs. 12 percent for patients who had emergency surgery (7).

When necessary, other faulty heart valves can be surgically repaired or replaced. After any valve replacement surgery, the individual must take anti-clotting medication for life, because blood tends to clot when it comes in contact with artificial valves.

Individuals with Marfan syndrome who have had surgery to replace a heart valve or have certain heart abnormalities are prone to heart wall or heart valve infections (8). They must be treated with oral antibiotics to prevent infection before dental procedures (including cleaning, filling and extractions) that may release bacteria into the blood stream. All individuals with Marfan syndrome should check with their cardiologist to see if they need antibiotics before dental procedures (1).

Sometimes individuals with Marfan syndrome who have had repair of the upper portion of the aorta have enlargement of other parts of their aortas. These individuals need to be followed with serial echocardiograms and a CT scan or MRI of the chest, abdomen and pelvis at least yearly. In some cases, surgical repair may be needed.

How are skeletal problems treated?
Children and adolescents with Marfan syndrome are monitored yearly for signs of scoliosis. Many develop mild scoliosis, which may not require treatment.

In more severe or progressive cases, scoliosis can cause back pain and shortness of breath. In these cases, a brace or surgery is recommended. Bracing can sometimes halt the progression of scoliosis, although sometimes surgery is needed to correct the deformity.

Chest wall (pectus) abnormalities also can interfere with breathing. Corrective surgery can be performed to alleviate these symptoms.

How are eye problems treated?
Children and adults with Marfan syndrome should have a yearly eye examination by an ophthalmologist. Most eye problems, such as nearsightedness, can be corrected with glasses or contact lenses. Early treatment for cataracts and glaucoma usually can prevent or lessen vision problems. Detached retinas can be treated with lasers.

Can individuals with Marfan syndrome exercise?
Most individuals can benefit from mild forms of exercise. However, strenuous exercise can place stress on the aorta. Therefore, children and adults with Marfan syndrome should avoid strenuous exercise, including competitive, collision and contact sports (1, 3, 4). Heavy lifting also should be avoided. With their doctor’s guidance, many can participate in less vigorous activities, such as walking, slow jogging, playing golf, leisurely bicycle riding, swimming and slow-paced tennis (1).

What causes Marfan syndrome?
Marfan syndrome is caused by mutations (changes) in one member of a pair of genes called the fibrillin genes. These genes are located on chromosome 15, one of the 23 pairs of human chromosomes.

Normally, the fibrillin gene enables the body to produce fibrillin, a protein that is a crucial component of connective tissue. Fibrillin normally is an abundant component of the connective tissue found in the aorta, in the ligaments that hold the eye’s lenses in place, in bones and in the lungs.

Mutations in the fibrillin gene lead to the formation of insufficient or faulty fibrillin, which probably weakens connective tissue. Fibrillin also helps regulate the levels of a growth factor (called transforming growth factor-beta) that plays a role in tissue growth and repair. Recent studies suggest that excessive amounts of this growth factor are released in individuals with Marfan syndrome, contributing to the signs and symptoms of the disorder (2, 4).

How is Marfan syndrome inherited?
The mutated fibrillin gene usually is inherited from one parent who has Marfan syndrome. The mutation is a dominant genetic trait. This means that each child of a parent with Marfan syndrome has a 50 percent chance of inheriting the mutation and a 50 percent chance of not inheriting it. Only those children who inherit the mutation develop the signs and symptoms of Marfan syndrome.

About 25 percent of cases of Marfan syndrome are sporadic (1, 2). This means that they are caused by a new mutation that occurred by chance in one of the fibrillin genes in a sperm or egg cell of an unaffected parent. Parents who themselves do not have Marfan syndrome and do not have a family history of Marfan syndrome, but who have an affected child, should meet with a genetic counselor to discuss their risks in another pregnancy.

As with other inherited disorders, Marfan syndrome cannot be caught from another person. Although it may be diagnosed at any age, the signs and symptoms of Marfan syndrome do not occur unless the person has the mutation.

Is pregnancy risky for women with Marfan syndrome?
There are several important issues for women with Marfan syndrome who are considering pregnancy. There is a 50 percent chance of having a child with Marfan syndrome with each pregnancy. In addition, the stress of pregnancy may cause rapid enlargement of the aorta, especially if the aorta is significantly enlarged before pregnancy (1, 3, 4). The risk of the aorta tearing is low, but not zero, in women with Marfan syndrome who have a normal aortic size. The risk increases during pregnancy as the aorta enlarges.

Women with Marfan syndrome should consult their health care providers and their cardiologist before pregnancy to discuss whether pregnancy is safe for them. The cardiologist generally recommends an echocardiogram to determine the dimensions of the aorta.

During pregnancy, an affected woman should receive prenatal care from a high-risk obstetrician who has experience with Marfan syndrome. She should also see her cardiologist regularly. She needs to have an echocardiogram in the first, second and third trimesters to monitor the size of her aorta (1, 3). If the aorta measures less than 4 cm, there is a low risk of tears during pregnancy (1, 4).

Women who are taking a beta-blocker generally can safely continue taking the medication throughout pregnancy. Those who have had a valve replaced usually are on an oral blood thinner called coumadin (warfarin). Because this drug increases the risk of birth defects, pregnant women are switched to another blood thinner called heparin, which is given by injection (usually two or three times a day), during pregnancy.

Women with Marfan syndrome do not appear to have an increased risk of miscarriage (1). Most women with Marfan syndrome can have a vaginal delivery. The doctor will take appropriate measures to lessen the stress of labor and birth. However, if the woman has significant aortic dilation, a cesarean birth may be recommended (1).

A woman with Marfan syndrome should have a follow-up echocardiogram at 1 to 2 months after delivery to check the size of her aorta (1).

Can Marfan syndrome be prevented?
At present, there is no way to prevent Marfan syndrome. Early diagnosis can help prevent serious complications. Genetic counseling enables informed decisions about childbearing and provides up-to-date information about the genetic basis of Marfan syndrome and genetic testing for this condition.

What research is being done on Marfan syndrome?
In 1991, researchers funded, in part, by the March of Dimes, discovered the gene that causes Marfan syndrome and identified the protein controlled by this gene (9). Since then scientists have discovered more than 1,000 mutations within the fibrillin gene (4). Researchers are learning more about the role the fibrillin gene plays in the growth and development of connective tissue. A clinical trial that started in 2007 is comparing the effectiveness of two different medicines in preventing or decreasing the rate of progression of aortic dilation (5).

For more information

References

  1. National Marfan Foundation. Living With Marfan Syndrome. Accessed 12/5/08.
  2. Pearson, G.D., et al. Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on Research in Marfan Syndrome and Related Disorders. Circulation, volume 118, number 7, August 12, 2008, pages 785-791.
  3. National Heart, Lung and Blood Institute. Marfan Syndrome. Accessed 12/1/08.
  4. Keane, M.G. and Pyeritz, R.E. Medical Management of Marfan Syndrome. Circulation, volume 117, number 21, May 21, 2008, pages 2802-2803.
  5. Brooke, B.S., et al. Angiotensin II Blockade and Aortic-Root Dilation in Marfan’s Syndrome. New England Journal of Medicine, volume 358, number 26, June 26, 2008, pages 2787-2795.
  6. Ahimastos, A.A., et al. Effect of Perindopril on Large Artery Stiffness and Aortic Root Diameter in Patients With Marfan Syndrome. Journal of the American Medical Association, volume 298, number 13, October 3, 2007, pages 1539-1547.
  7. Gott, V.L., et al. Replacement of the Aortic Root in Patients with Marfan’s Syndrome. New England Journal of Medicine, volume 340, number 17, April 29, 1999, pages 1307-1313.
  8. American Heart Association. Marfan Syndrome. Accessed 11/26/08.
  9. Lee, B., et al. Linkage of Marfan Syndrome and a Phenotypically Related Disorder to Two Different Fibrillin Genes. Nature, volume 352, July 25, 1991, pages 330-334.

January 2009

Neural tube defects

Neural tube defects (NTDs) are birth defects of the brain and spinal cord. They happen in about 3,000 pregnancies each year in the United States.

A baby’s neural tube normally develops into the brain and spinal cord. It starts out as a tiny, flat ribbon that turns into a tube by the end of the first month of pregnancy. NTDs happen if the tube doesn’t close completely. NTDs can cause serious problems for babies, including death.

If women of childbearing age take 400 micrograms of folic acid every day before and during early pregnancy, it may help reduce their baby's risk for NTDS. Folic acid is a B vitamin that every cell in your body needs for normal growth and development.

What is spina bifida?
Spina bifida is the most common NTD. It affects about 1,500 babies a year in this country. In this condition, the tiny bones of the vertebrae do not close completely, and a part of the spinal cord pokes through the spine.

Spina bifida sometimes can be treated with surgery before or after birth. But children with spina bifida may have paralyzed legs and problems controlling their bladder and bowel (going to the bathroom). There also are milder forms of spina bifida that cause fewer problems for children.

What is anencephaly?
Anencephaly is one of the most severe NTDs. It affects about 1,000 babies each year in this country. Babies with this condition are missing major parts of the brain, skull and scalp. They do not survive long after birth, usually for just a few hours.

Anencephaly occurs when the upper part of the neural tube that forms the brain does not close completely. Babies with this condition often have other birth defects of the head and face, as well as defects in other parts of the body.

Girls are three times more likely than boys to have anencephaly.

What is an encephalocele?
Encephalocele is a rare NTD that affects the brain and skull. About 375 babies are born with this NTD in the United States each year.

In this condition, a sac that contains the membranes that cover the brain pokes through an opening in the skull. Often, part of the brain pokes through, too. These conditions usually happen:

  • At the base of the skull where it meets the neck (the most common site)
  • Between the forehead and nose
  • In middle of the upper part of the skull

Babies with encephalocele generally need surgery to place parts of the brain back inside the skull and close the opening.

Some babies have a build-up of fluid in the brain. This is called hydrocephalus. Babies with this condition are treated with surgery to insert a tube (called a shunt) into the brain. The shunt drains excess fluid. The shunt runs under the skin into the chest or abdomen, and the fluid passes into the child’s body. The fluid does not hurt other parts of the child’s body.

The outlook for children with encephalocele depends on the location of the opening, the parts of the brain that are affected, and whether or not they have other birth defects. At least half of all children with encephalocele have other birth defects, including defects of the head and face. About 20 percent are stillborn. Stillborn means that a baby dies in the womb after 20 weeks of pregnancy but before birth.

Lasting disabilities for children with encephalocele can include:

  • Intellectual disabilities. These happen in about 75 percent of children with encephalocele. The remaining 25 percent may have normal intelligence.
  • Movement problems or paralysis (not being able to move)
  • Vision problems
  • Seizures

What causes NTDs?
We’re not exactly sure what causes NTDs. There may be one or several causes, including:

  • Genetics. This means a baby inherits the condition from his parents. Parents pass traits like eye and hair color and sometimes birth defects to their children through genes.
  • Environment. This is things that you come in contact with in everyday life. Some can be harmful to a pregnancy, like air pollution, lead and cigarette smoke.

Who is at risk of having a baby with an NTD?
Anyone can have a baby with an NTD. But some are more likely than others:

  • Couples with a family history of NTDs. This means you’ve already had a baby with an NTD or someone in your family has had a baby with an NTD. A couple with one child with an NTD has a 4 out of 100 chance (4 percent) of having another baby with an NTD. A couple with two affected children has a 1 in 10 chance (10 percent) chance of having another baby with an NTD. If you have a family history of NTDs, see a genetic counselor to discuss risks of NTDs to your future children.
  • Women who take certain anti-seizure medications. If you take medicine to prevent seizures, talk to your health care provider before you get pregnant about how the medicine may affect your pregnancy.
  • Women who are obese. Some studies show that being obese increases your risk for having a baby with an NTD. Talk to your provider about getting to a healthy weight before pregnancy.
  • Women who have diabetes. Diabetes is a medical condition in which your body has too much sugar (called glucose) in their blood.
  • Certain groups of people. In North America, Hispanics are at highest risk of having a baby with an NTD, followed by whites. NTDs are less common among Ashkenazi Jews, blacks and most Asians.

How can you help prevent NTDs in your baby?
Taking the B-vitamin folic acid can help prevent NTDs. It’s important to have enough folic acid in your system before pregnancy and during early pregnancy, before the neural tube closes.

The March of Dimes recommends that all women of childbearing age take a multivitamin with at least 400 micrograms of folic acid every day before pregnancy and during early pregnancy. You can take up to 1,000 micrograms each day. But don’t take more than 1,000 micrograms unless you talk to your provider first.

You need folic acid when you’re pregnant, too. During pregnancy, take a prenatal vitamin that has at least 600 micrograms of folic acid in it every day.

If you’ve already had a pregnancy affected by an NTD, you need even more folic acid. Take at least 4,000 micrograms of folic acid each day, starting at least 1 month before pregnancy and during the first trimester of pregnancy. Studies show that taking this amount before and during early pregnancy can help reduce your risk of having another baby with an NTD by about 70 percent. Women with spina bifida, diabetes or seizure disorders also need this much folic acid every day. Talk to your provider about how to get this much folic acid.

Can you get folic acid from food?
Yes, you can get folic acid from the foods you eat. Some flour, breads, cereals and pasta have folic acid added to them. Look for the words “enriched,” “fortified” or “folic acid” on the package to know if the product has folic acid in it. Corn products, like corn tortillas and corn meal, are not fortified with folic acid now. But they may be in the future.

You also can get folic acid from some fruits and vegetables. When folic acid is naturally in a food, it’s called folate Good sources of folate are:

  • Beans
  • Leafy green vegetables
  • Orange juice

You have to eat a lot of these foods to get the right amount of folic acid every day. So even if you eat them, remember to take your vitamin, too.

Can NTDs be detected before birth?
Yes. Health care providers routinely offer pregnant women screening tests to help identify babies that are at increased risk of having an NTD. These screening tests include:

  • Quad screen. This blood test measures four substances in a mother’s blood to tell if her pregnancy is at an increased risk of having an NTD, other than encephalocele.
  • Ultrasound. This test can help detect pregnancies at increased risk of encephalocele and other NTDs.

If a screening test shows an increased risk of NTDs, your provider may recommend additional tests, such as amniocentesis and a detailed ultrasound of the baby’s skull and spine.

What are the benefits of detecting an NTD before birth?
If an NTD is diagnosed early in pregnancy, you can talk to your health care provider to learn more about your baby’s condition and birth and treatment options. For example:

  • You can plan to have your baby in a medical center that specializes in caring for babies with NTDs. This way your baby can have any necessary surgery or treatment soon after birth.
  • You can talk to your provider about whether a vaginal or cesarean birth is better for your baby.
  • Your baby may be able to have surgery to repair spina bifida before birth, while still in the womb. More than 400 babies have had this kind of surgery. Research shows that surgery on a baby to repair spina bifida while still in the womb is more effective than surgery after birth.

Does the March of Dimes support research on NTDs?
Yes. A number of researchers supported by the March of Dimes are looking for genes that may contribute to NTDs. Others are working to better understand how folic acid prevents NTDs.

For more information
American Academy of Pediatrics
Spina Bifida Association
Centers for Disease Control and Prevention

Last reviewed November 2012

See also: Your first prenatal checkup, Later prenatal checkups

Neurofibromatoses

Neurofibromatoses (NF) are genetic disorders of the nervous system that cause tumors to grow on nerves. These tumors are benign, which means they are not cancer. NF also can cause abnormalities of skin and bone. The severity of symptoms varies greatly.

There are three main forms of NF:

  1. NF1, formerly called peripheral neurofibromatosis or von Recklinghausen’s disease
  2. NF2, formerly called bilateral acoustic neurofibromatosis, central neurofibromatosis or vestibular schwannoma
  3. Schwannomatosis, until recently considered a form of NF 2

How common is NF?
About 100,000 individuals in the United States have a NF (1). NF1 is most common. It affects about 1 in 3,000 births in the United States (1, 2).

NF2 is less common, affecting about 1 in 25,000 births (1, 3). Schwannomatosis affects about 1 in 40,000 births (4). All forms of NF are found in every racial and ethnic group throughout the world and affect both sexes equally.

What causes NF?
The three forms of NF are caused by abnormalities in three different genes. The gene for NF1 is located on chromosome 17. The genes for NF2 and schwannomatosis are located on chromosome 22.

NF1 and NF2 are inherited in the same way. In about 50 percent of cases, a child inherits the abnormal gene from one parent who has the disorder. In some cases, the affected parent may have such mild symptoms that he may not know he has the disorder. The remaining half of NF1 and NF2 cases are caused by new mutations (changes) in the genes (1). This means that NF1 or NF2 can occur in a person who has no family history of the condition. The abnormal gene in NF1 and NF2 is autosomal dominant, which means that any child of only one parent with NF has a 50-50 chance of inheriting the NF gene.

Less is known about how schwannomatosis is inherited. It appears that most cases (about 85 percent) are caused by new mutations (1, 5).

What are the signs of NF1?
According to the National Institutes of Health (NIH), there are seven common signs of NF1 (1). NF1 is diagnosed in individuals who have two or more of these signs:

  1. Six or more tan spots on the skin, called café-au-lait spots, that are wider than 1/5 inch before puberty or 3/5 inch after puberty. Café-au-lait means “coffee with milk” in French. These spots usually are present at birth or appear by age 2. Café-au-lait spots may increase in size and number and darken with age.
  2. Freckles that appear under the arms or in the groin, usually by 7 years of age.
  3. Two or more benign tumors under the skin. These are called neurofibromas. Neurofibromas grow on nerves. They usually develop at around the time of puberty, but they may develop at any age. An affected person may have any number of neurofibromas. A person also may have a single neurofibroma without having NF.
  4. A tumor on the optic (eye) nerve. This kind of tumor is called an optic glioma. It rarely causes vision problems. Most of these tumors, which are usually diagnosed by 7 years of age, cause no symptoms and require no treatment.
  5. Two or more tiny tan or brown Lisch nodules. These are small clumps of pigment that appear in the iris (colored part of the eye). These usually appear at around puberty and cause no vision problems.
  6. A variety of bone defects, such as bowing of the legs below the knee. These usually are present at birth or develop during the first year of life.
  7. A family history of NF1 in a parent, sibling or child..

How is NF1 diagnosed?
NF1 is diagnosed by physical examination. A health care provider may use a special lamp to check the skin so that he can see very light-colored café-au-lait spots. The provider may recommend tests, including X-rays, computerized tomography (CT scans) and magnetic resonance imaging (MRI). In some cases, genetic testing of a blood sample is needed to confirm the diagnosis. Some children under 8 years of age may have café-au-lait spots but no other signs of NF1. These children should be monitored carefully to see if other signs of the disorder
How does NF1 affect a person?

In many cases of NF1, symptoms are mild, and affected individuals live a normal life. Some signs of NF1, including café-au-lait spots, freckling and Lisch nodules, pose no risk to health. Other common characteristics, including short stature and large head size, also have little effect on health.

Some health problems that affect individuals with NF1 include:

  • Skin neurofibromas: Some individuals have many of these benign tumors on the face and body. These tumors generally are harmless, but an affected person may have trouble dealing with the way they look on the body.
  • Plexiform neurofibromas: These are deep neurofibromas that can grow inside the body and can affect many organ systems. These tumors affect about 30 percent of individuals with NF1 (6). Some plexiform neurofibromas cause no symptoms, but others can cause serious problems, depending on the organ system involved.
  • Learning disabilities: Up to 65 percent of children with NF1 have learning disabilities (6). These include hyperactivity and attention and language problems (1, 6).
    Scoliosis: Up to 25 percent of children with NF1 have scoliosis, which is progressive curvature of the spine. Scoliosis can begin at an early age (6).
  • Cardiovascular abnormalities: Individuals with NF1 have an increased risk of congenital heart defects, constricted or damaged blood vessels and high blood pressure (1, 6). In children, blood vessel abnormalities in the brain can sometimes cause headaches, seizures and weakness (6).
  • Bulging of the eye or vision problems: These problems affect a few individuals with optic glioma.
  • Cancer: In about 3 to 5 percent of affected people, one or more fibromas become malignant and require treatment with surgery, chemotherapy or radiation (1). Individuals with NF1 also appear to be at an increased risk of leukemia and certain rare cancers (2).

How is NF1 treated?
There is no cure for NF1, but there are ways to treat some of its effects. Painful or disfiguring skin tumors can be removed with surgery. However, they often grow back. Optic gliomas that affect vision can be treated with surgery and/or chemotherapy (6). Scoliosis may be treated by surgery or by wearing a brace. Bowed legs also may be treated by wearing a brace.

A number of multidisciplinary NF clinics throughout the United States address specific medical concerns and routine NF-related health care issues.

Researchers are developing drugs that target the underlying cellular defects in NF1, in order to help prevent or shrink nerve cell tumors. In the future, these new drugs may improve the treatment of NF1.

What are the signs of NF2?
Signs of NF2 include:

  • Vestibular schwannomas: These are benign tumors that grow on a nerve (called the 8th cranial nerve) that goes from the ear to the brain. These tumors are called schwannomas because they come from Schwann cells, which support and protect nerve cells. They often cause pressure on the acoustic (hearing) nerves, resulting in hearing loss. Almost all individuals with NF2 develop these tumors by age 30 (3).
  • Brain and spinal cord tumors: Many persons with NF2 develop benign tumors along nerve tissues elsewhere in the body, including the brain and spinal cord.
  • Cataracts: Many affected individuals develop a special type of cataract early in life. A cataract is a kind of film or cloud that covers the eye’s lens. They also may develop changes in the retina, which is the light-sensing tissue that lines the back of the eye.
  • Skin tumors: Persons with NF2 may have a small number of skin tumors (schwannomas). However, they have few or no café-au-lait spots or neurofibromas.

How is NF2 diagnosed?
As with NF1, NF2 usually is diagnosed by physical examination. The provider may recommend a number of imaging tests, including MRI, to look at the brain and spinal cord. MRI can detect tiny tumors, allowing for early diagnosis. In some cases, genetic testing is done to help confirm the diagnosis.

When NF2 is diagnosed, hearing tests called audiometry and brainstem auditory evoked response test are recommended. These tests help determine how well the 8th cranial nerve is working. The individual should be examined by an ophthalmologist (eye specialist) to look for cataracts and other eye problems that can contribute to vision loss.

How does NF2 affect a person?
Symptoms of NF2 usually appear in the teens or early twenties. Symptoms vary greatly in severity and can include (3, 5):

  • Hearing loss
  • Ringing in the ears
  • Dizziness
  • Facial numbness
  • Balance problems
  • Headaches
  • Vision loss
  • Numbness or weakness in parts of the body, such as the legs

How is NF2 treated?
As is the case in NF1, there is no cure for NF2, but surgery can help control symptoms. However, surgery on the 8th cranial nerve can sometimes cause additional hearing loss, so individuals and families must carefully weigh the risks and benefits of surgery. MRI scans can detect very small tumors, sometimes allowing for early treatment.

Several medical centers are examining the effectiveness of stereotactic radiosurgery in treating vestibular schwannomas associated with NF2 (7). In this treatment, a high dose of radiation is delivered precisely to the tumor without exposing the surrounding tissue to significant radiation. It is not yet known whether this treatment increases the risk of cancer.

A small, preliminary study found that a cancer drug called bevacizumab (Avastin) shrank vestibular schwannomas and improved hearing in some, but not all, individuals. However, more studies are needed on the safety and effectiveness of this treatment (8).

Spinal cord tumors also can be removed surgically, when necessary. However, many of these tumors grow slowly and produce few or no symptoms. In such cases, the health care provider monitors the tumors with imaging tests.

When is NF1 or NF2 testing recommended for couples planning pregnancy?
Some women and men planning pregnancy may not know that they have NF1 or NF2. They may have very mild symptoms that have gone undiagnosed, or they may not have developed symptoms. In such cases, a family health history done during a preconception or early prenatal visit can help identify couples at increased risk of having a baby with NF. The health care provider may suggest testing for NF1 or NF2 if an individual:

  • Has a child with possible signs of NF
  • Has a family history of NF in a parent, sibling or child
  • Has a personal or family history of NF-related conditions, such as skin tumors, freckling (in a NF1-related pattern) or hearing loss

If a woman or her partner is found to have NF1 or NF2, they should consider consulting a genetic counselor. Genetic counselors can help a family understand the chances of a birth defect occurring in a pregnancy and can discuss the possibility of prenatal testing. Genetic counseling is available at most large medical centers and teaching hospitals. To find a genetic counselor in their area, individuals can ask their health care provider or contact the National Society of Genetic Counselors.

What are the signs and symptoms of schwannomatosis?
Affected individuals develop schwannomas, as do many people with NF2. However, the schwannomas do not develop on the 8th cranial nerves, so affected individuals do not develop hearing loss. The main symptom of schwannomatosis is pain, which can occur in any part of the body (3). Affected individuals also may have other neurological problems, such as numbness, tingling or weakness in fingers and toes.

How is schwannomatosis diagnosed?
As with NF1 and NF2, schwannomatosis is diagnosed with a physical examination. Imaging tests, such as MRI, often are used to rule out vestibular schwannomas and NF2.

How is schwannomatosis treated?
Schwannomas often can be surgically removed to relieve pain, though tumors sometimes grow back. Affected individuals also can be treated with pain medications.

Do neurofibromatoses affect pregnancy?
Most women with NF1 have healthy pregnancies. However, neurofibromas may increase in size and number during pregnancy, apparently because of hormonal changes. This sometimes may contribute to pregnancy complications, such as compression of the umbilical cord or obstruction of the birth canal (requiring cesarean section) (2). Pregnant women with NF1 also may be at increased risk of high blood pressure (2). A pregnant woman with NF1 should be cared for by an obstetrician who is familiar with NF1, in close consultation with her NF specialist.

There is little information on the effects of NF2 or schwannomatosis on pregnancy. Women with NF2 and spinal tumors may need imaging tests before labor and birth to make sure it’s safe for them to have epidural anesthesia (3).

Is genetic testing available to help diagnose neurofibromatosis?
Yes, for NF1 and NF2. Though NF1 and NF2 usually are diagnosed with a physical examination, providers sometimes use genetic testing to help confirm the diagnosis. Genetic testing can be conducted before birth to help identify individuals who don’t show symptoms but have a family history of these disorders. However, genetic tests cannot predict the degree of severity of either form of NF. There is no definitive genetic test available now for schwannomatosis.

Does the March of Dimes conduct research on NF?
The March of Dimes has funded NF studies, including basic research on the causes of these and other nervous system diseases. For example, researchers are studying genetically controlled events in the embryo that are crucial to development of the body’s nervous system and factors that regulate growth and maintenance of nerves. One grantee is seeking to determine how mutations in the NF1 gene cause bone abnormalities such as scoliosis, in order to develop drugs to help prevent them.


Where can I get further information about NF?

References

  1. National Institutes of Neurological Disorders and Stroke (NINDS). (2009). Neurofibromatosis fact sheet.
  2. Friedman, J.M. (2009). Neurofibromatosis 1. Gene Reviews. University of Washington at Seattle.
  3. Evans, D.G. (2009). Neurofibromatosis 2. Gene Reviews. University of Washington at Seattle.
  4. Children’s Tumor Foundation. (2009). Living with NF: Schwannomatosis.
  5. Lu-Emerson, C. & Plotkin, S.R. (2009). The neurofibromatoses. Part 2: NF2 and schwannomatosis. Reviews in Neurological Diseases, 6 (3), E81-E86.
  6. Williams, V.C., Lucas, J., Babcock, M.A., Gutmann, D.H., Korf, B. & Maria, B.L. (2009). Neurofibromatosis type 1 revisited. Pediatrics, 123 (1), 123-133.
  7. Asthagiri, A.K., Parry, D.M., Butman, J.A., Kim, H.J., Tsilou, E.T., et al. (2009). Neurofibromatosis type 2. Lancet, 373, 1974-1986.
  8. Plotkin, S.R., Stemmer-Rachamimov, A.O., Barker, F.G., Halpin, C., Padera, T.P., et al. (2009). Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. New England Journal of Medicine, 361 (4), 358-367.

May 2010

PKU (Phenylketonuria) in your baby

Phenylketonuria (also called PKU) is a condition in which your body can’t break down an amino acid called phenylalanine. Amino acids help build protein in your body. Without treatment, phenylalanine builds up in the blood and causes health problems.

In the United States, about 1 in 10,000 to 15,000 babies is born with PKU each year. The illness happens in all ethnic groups. But it’s more common in people who are Native American and Northern European than those who are African-American, Ashkenazi Jewish or Japanese.

What causes PKU?
PKU is inherited. This means it’s passed from parent to child through genes. A gene is a part of your body’s cells that stores instructions for the way your body grows and works. Genes come in pairs—you get one of each pair from each parent.

Sometimes the instructions in genes change. This is called a gene change or a mutation. Parents can pass gene changes to their children. Sometimes a gene change can cause a gene to not work correctly. Sometimes it can cause birth defects or other health conditions. A birth defect is a health condition that is present in a baby at birth.

Your baby has to inherit a gene change for PKU from both parents to have PKU. If she inherits the gene from just one parent, she has the gene change for PKU, but she doesn’t have PKU. When this happens, your baby is called a PKU carrier. A PKU carrier has the gene change but doesn’t have PKU.

How do you know if your baby has PKU?
All babies have a newborn screening test for PKU. Newborn screening checks for serious but rare conditions at birth. It includes blood, hearing and heart screening. With newborn screening, PKU can be found and treated early so babies can grow up healthy.

Before your baby leaves the hospital, his health care provider takes a few drops of blood from his heel. The blood is collected on a special paper and sent to a lab for testing. The lab then sends the results back to your baby’s provider.

If newborn screening results aren’t normal, it simply means your baby needs more testing. Your baby’s provider can recommend another kind of test, called a diagnostic test. This test can check to see if your baby has PKU or if there is some other cause for abnormal test results.

If your baby is tested before he’s a full day old, it’s possible for the test to miss PKU. Some experts recommend that if your baby was tested within the first 24 hours of life, he should be tested again at 1 to 2 weeks of age.

What problems can PKU cause?
Babies born with PKU seem normal for the first few months of life. But without treatment, they begin to have signs and symptoms of the illness at about 6 months of age. These include:

  • Jerky movements in arms and legs
  • Lighter skin and eyes (Babies with PKU can’t properly make melanin, the pigment in the body that’s responsible for skin and hair color.)
  • Musty body smell
  • Seizures
  • Skin rashes
  • Small head size
  • Taking longer than expected to sit, crawl or walk
  • Losing interest in surroundings
  • Delays in mental and social skills
  • Intellectual disabilities
  • Behavior problems, like being hyperactive

If your baby has PKU, what kind of treatment does he need?
If your baby has PKU, he may need testing as often as once a week or more often for the first year of life to check his phenylalanine levels. After that, he may have testing once or twice a month throughout childhood.

Your baby needs to follow a special meal plan that is low in phenylalanine. It’s best to start this meal plan as soon as possible, ideally within the first 7 to 10 days of life.

At first, your baby gets a special protein formula that has reduced phenylalanine. Protein is important to help your baby grow and develop. The amount of phylalanine in the formula is controlled to meet you baby’s individual needs. Your baby also can have some breast milk. Your breast milk has phenylalanine in it, so talk to your baby’s provider to find out how much breast milk your baby can have.

When your baby is ready to eat solid foods, she can eat vegetables, fruits, some grains (like low-protein cereals, breads and pasta) and other low-phenylalanine foods. If your baby has PKU, she should not eat:

  • Milk, cheese, ice cream and other dairy products
  • Eggs
  • Meat and poultry
  • Fish
  • Nuts
  • Beans
  • Food or drinks that contain aspartame. This is an artificial sweetener that has lots of phenylalanine in it. It’s sold as NutraSweet® and Equal®.

PKU meal plans are different for each baby and can vary over time depending on how much phenylalanine your baby can take. Health care providers at a medical center or clinic that has a special program to treat PKU can help you create a PKU meal plan for your baby. Ask your baby’s health care provider for information on a medical center or clinic that treats PKU.

Your child follows the PKU meal plan through her whole life. If she eventually gets pregnant, she follows her meal plan throughout pregnancy. Most pregnant women who have PKU can have healthy pregnancies and healthy babies.

The medicine Kuvan® (sapropterin dihydrochloride) can help some people with PKU. The medicine is more likely to work in people with mild or special forms of PKU. Children who take Kuvan® must follow a special meal plan, but it may not be as strict as one for those not taking the drug. They still need regular blood tests to check phenylalanine levels.

For more information
National PKU News
Serum phenylalanine screening
Genetics Home Reference: PKU
MedlinePlus: PKU

Last reviewed February 2013

See also: Genetic counseling, Newborn screening

Rare birth defects

A birth defect is a health condition that is present at birth. Birth defects may change the shape or function of one or more parts of the body. They can cause problems in overall health, how the body develops, or how the body works. One in 33 babies in the United States is born with a birth defect.

We don’t know the cause of all birth defects. Some may be caused by the genes we inherit from our parents. Others may be caused by environmental factors, like exposure to harmful chemicals. Some may be caused by a combination of genes and environment. In most cases, the causes are unknown.

There are thousands of different birth defects. The most common are heart defects, cleft lip and palate, Down syndrome and spina bifida. Others, such as the ones listed below, are rare and less well known. Use the links to find out more information about these birth defects. Or visit the Office of Rare Disease Research or Genetics Home Reference.

Last reviewed February 2012

Rh disease

The Rh factor is an inherited protein found on the surface of red blood cells. Most people have this protein and are called Rh-positive. However, some people don't have protein; they are called Rh-negative. Rh-negative pregnant women are at risk of having a baby with a potentially dangerous form of anemia called Rh disease. Fortunately, treatment usually can prevent Rh disease.

How does Rh disease affect a fetus or newborn?
Rh disease destroys fetal red blood cells. It once was a leading cause of fetal and newborn death. Without treatment, severely affected fetuses often are stillborn. In the newborn, Rh disease can result in jaundice (yellowing of the skin and eyes), anemia, brain damage, heart failure and death. It does not affect the mother’s health.

How many people are Rh-negative?
In the United States, about 15 percent of the white population, 5 to 8 percent of the African-American and Hispanic populations, and 1 to 2 percent of the Asian and Native American populations are Rh-negative (American College of Obstetricians and Gynecologists [ACOG], 2006; Moise, 2009). Being Rh-negative does not affect a person’s health in any way.

What causes Rh disease?
An Rh-negative mother and an Rh-positive father may conceive an Rh-positive baby. When this occurs, some of the fetus’s Rh-positive red blood cells may get into the mother’s bloodstream during pregnancy, labor and birth. Because red blood cells containing the Rh factor are foreign to the mother’s system, her body tries to fight them off by producing antibodies against them. This is called sensitization.

Once a woman becomes sensitized, her Rh antibodies can cross the placenta and destroy some of the red blood cells of an Rh-positive fetus. In a first pregnancy with an Rh-positive baby, there usually are no serious problems because the baby often is born before the mother is sensitized, or at least before the mother produces many Rh antibodies. However, a sensitized woman continues to produce Rh antibodies throughout her life. This means that in a second or later pregnancy, an Rh-positive baby is at risk for more severe Rh disease.

How can a woman find out if she is Rh-negative?
A simple blood test can tell if a woman is Rh-negative. Every woman should be tested at her first prenatal visit, or before pregnancy, to find out if she is Rh-negative. Another blood test can show if an Rh-negative woman has become sensitized.

How can Rh disease be prevented?
An unsensitized Rh-negative pregnant woman can be treated with injections (shots) of a purified blood product called Rh immune globulin (RhIg) to prevent sensitization. She most likely receives RhIg at 28 weeks of pregnancy and again within 72 hours of giving birth if a blood test shows that her baby is Rh-positive (ACOG, 1999). She does not need an injection after delivery if her baby is Rh-negative. Some health care providers recommend an additional RhIg injection if a woman’s pregnancy goes past her due date (ACOG, 1999; Moise, 2008).

An Rh-negative woman should be treated with RhIg after any situation in which the fetal red blood cells can mix with her blood, including (ACOG, 1999; Moise, 2008):

Do all unsensitized Rh-negative women need treatment with RhIg?
An Rh-negative woman does not need treatment with RhIg if blood tests show that the baby’s father is Rh-negative (ACOG, 1999). If the father is Rh-negative, the baby is Rh-negative. An Rh-negative baby is not at risk of Rh disease.

How does RhIg work?
It is not known exactly how RhIg works. It contains antibodies to the Rh factor that may prompt certain immune cells to clear Rh-positive cells from the mother’s circulation. As a result, she may not produce her own antibodies against fetal Rh-positive cells (Moise, 2008).

Protection by RhIg lasts only about 12 weeks (ACOG, 1999). An Rh-negative woman must be treated during each pregnancy.

Does RhIg treatment always work?
Proper treatment with RhIg can prevent sensitization in almost all unsensitized Rh-negative women (ACOG, 1999). However, RhIg does not work for an Rh-negative woman who already is sensitized. The main reason Rh-negative women become sensitized is that they do not receive treatment when they need it, such as after an unrecognized miscarriage.

Is there any way to get rid of a sensitized mother’s antibodies?
No. Even if a woman has no symptoms and stays healthy, she can continue to produce antibodies as part of her blood. If she has any more Rh-positive babies, they could develop Rh disease.

What special treatment does a sensitized Rh-negative woman need during pregnancy?
The baby’s father can have a blood test to see whether he is Rh-positive or Rh-negative. If the father is Rh-negative, the baby is not at risk of Rh disease, and the pregnant woman does not need any special tests or treatment.

If the father is Rh-positive (or if his Rh status is not known), the health care provider usually offers a sensitized pregnant woman a test called amniocentesis to determine whether the baby is Rh-positive or Rh-negative. Even if the father is Rh-positive, he may carry an Rh-negative gene. The baby has a 50-percent chance of inheriting the Rh-negative gene, so he has a 50-percent chance of being Rh-negative. During amniocentesis, the doctor inserts a needle into a woman’s abdomen to withdraw a small amount of amniotic fluid for testing. Amniocentesis poses a very small risk of miscarriage.

A new maternal blood test appears to be highly accurate in determining whether the fetus is Rh-positive or negative (5). This blood test was recently introduced in the United States and may soon reduce the need for amniocentesis (Van der Schoot, Hahn & Chitty, 2008).

If the fetus is Rh-positive (or if the fetal Rh status is unknown), the health care provider measures the levels of antibodies in the mother’s blood as pregnancy progresses. If she develops high levels of antibodies, the provider recommends tests that can help determine if the baby is developing Rh disease.

Which tests are used to monitor the baby’s health?
Most major medical centers offer an examination with a special form of ultrasound, called Doppler ultrasound, to determine if the fetus is developing anemia and how severe it may be. This test, which is repeated every 1 to 2 weeks, measures the speed of blood flowing through an artery in the fetus. It poses no risk to the fetus. Doppler ultrasound has reduced the need for amniocentesis to monitor fetuses at risk of Rh disease. A 2006 study reported that a Doppler ultrasound is more accurate than amniocentesis in detecting anemia (Oepkes, 2006). However, this test is not yet available everywhere. Women who do not live near a medical center that offers Doppler ultrasound can still be monitored with amniocentesis, which must be repeated every 10 days to 2 weeks.

If Doppler ultrasound or amniocentesis shows that the fetus may be developing severe anemia, the health care provider may recommend another test called cordocentesis. In this test, the doctor inserts a thin needle through the mother’s abdomen, guided by ultrasound, into a tiny blood vessel in the umbilical cord to take a blood sample from the fetus. This test poses a small risk of miscarriage.

How are fetuses and newborns with Rh disease treated?
If the fetus is near term and tests show that the baby is developing anemia, the health care provider may recommend inducing labor early, before the mother’s antibodies destroy too many fetal blood cells. After birth, if the baby has jaundice, he may be placed under special blue lights (phototherapy). In some cases, the baby may need a blood transfusion. Some cases of Rh disease are so mild that the baby does not need any treatment.

About 10 percent of fetuses with Rh disease develop severe anemia, which in the past was usually fatal (Mari et al., 2000). Today these fetuses can be treated in the uterus as early as 18 weeks gestation with blood transfusions, which are given using cordocentesis. About 90 percent of treated babies now survive (Moise, 2008).

Can the RhIg treatment transmit HIV or hepatitis?
Although RhIg is a blood product, there is minimal to no risk of contracting HIV or hepatitis from it (ACOG, 1999). The donated blood is screened for HIV and hepatitis and treated with a substance that kills viruses and bacteria.

References

  1. American College of Obstetricians and Gynecologists (ACOG). (1999). Prevention of RhD alloimmunization (Practice Bulletin No. 4). Washington, D.C.: Author.
  2. American College of Obstetricians and Gynecologists (ACOG). (2006). Management of alloimmunization during pregnancy. (Practice Bulletin No. 75). Washington, D.C.: Author.
  3. Lenetix Medical Screening Laboratory. RhD genotyping. Retrieved September 11, 2009 from: http://www.lenetix.com./html/rhd__sry_genotyping.html.
  4. Mari, G., et al. (2000). Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. New England Journal of Medicine, 342(1), 9-14.
  5. Moise, K.J. (2008). Management of Rh immunization in pregnancy. Obstetrics and Gynecology, 112(1), 164-176.
  6. Moise, K.J. (2009). Hemolytic disease of the fetus and newborn. In Creasy, R.K., et al (eds.), Creasy and Resnik’s maternal-fetal medicine principles and practice (6th ed., pages 477-503). Philadelphia: Saunders Elsevier.
  7. Oepkes, D. (2006). Doppler ultrasonography versus amniocentesis to predict fetal anemia. New England Journal of Medicine, 355(2), 156-164.
  8. Van der Schoot, C.E., Hahn, S. & Chitty, L.S. (2008). Non-invasive prenatal diagnosis and determination of fetal Rh status. Seminars in Fetal and Neonatal Medicine, 13, 63-68.

December 2009

Sickle cell disease and your baby

Sickle cell disease (also called SCD) is a condition in which the red blood cells in your body are shaped like a sickle (like the letter C). Red blood cells carry oxygen to the rest of your body. In a healthy person, red blood cells are round and flexible. They flow easily in the blood. A person with SCD has red blood cells that are stiff and can block blood flow. This can cause pain, infections and, sometimes, organ damage and strokes.

SCD is a kind of anemia. Anemia happens when you don’t have enough healthy red blood cells to carry oxygen to the rest of your body.

In the United States, SCD is most common among blacks and Hispanics. SCD affects about 1 in 500 black births and about 1 in 36,000 Hispanic births in this country. SCD is also common among people with family from Africa, the Caribbean, Greece, India, Italy, Malta, Sardinia, Saudi Arabia, Turkey or South or Central America.

If your baby is born with SCD, he may be generally healthy or he may need special care throughout his life.

What causes SCD?
SCD is inherited. This means it’s passed from parent to child through genes. A gene is a part of your body’s cells that stores instructions for the way your body grows and works. Genes come in pairs—you get one of each pair from each parent.

Sometimes the instructions in genes change. This is called a gene change or a mutation. Parents can pass gene changes to their children. Sometimes a gene change can cause a gene to not work correctly. Sometimes it can cause birth defects or other health conditions. A birth defect is a health condition that is present in a baby at birth.

Your baby has to inherit a gene change for sickle cell from both parents to have SCD. If he inherits the gene change from just one parent, he has sickle cell trait. This means that he has the gene change for SCD, but he doesn’t have SCD. When this happens, he’s called a carrier. A carrier has the gene change but doesn’t have the condition.

Sickle cell trait cannot become SCD. A few people with sickle cell trait show signs of SCD, but this is unusual. Most don’t.

Are there different kinds of SCD?
Yes. Common kinds of SCD are:

  • Sickle cell anemia (also called hemoglobin SS). Hemoglobin is the part of red blood cells that carries oxygen to the rest of the body. Sickle cell anemia is caused when a baby gets one sickle cell gene change from each parent.
  • Hemoglobin SC. This condition is caused when a baby gets one sickle cell gene change from one parent and one gene change for hemoglobin C (another abnormal type of hemoglobin) from the other parent.
  • Hemoglobin S-beta thalassemia. This condition is caused when a baby gets a sickle cell gene change from one parent and a gene change for beta thalassemia from the other parent. Thalassemia is another kind of anemia.

How do you know if your baby has SCD or sickle cell trait?
All babies have a newborn screening test for SCD. Newborn screening checks for serious but rare and mostly treatable conditions at birth. It includes blood, hearing and heart screening. With newborn screening, SCD can be found and treated early.

Before your baby leaves the hospital, his health care provider takes a few drops of blood from his heel. The blood is collected and dried on a special paper and sent to a lab for testing. The lab then sends the results back to your baby’s provider.

If newborn screening results aren’t normal, it simply means your baby needs more testing. Your baby’s provider can recommend another kind of test, called a diagnostic test. This test can check to see if your baby has SCD or if there is some other cause for abnormal test results.

What problems can SCD cause?
Some children with SCD may be generally healthy, while others may need special care. The most common health problems related to SCD are:

Acute chest syndrome. This condition is very serious and painful. It’s caused by an infection and/or blocked blood flow in the lungs. Signs and symptoms include breathing problems, chest pain and fever. Your child’s provider may recommend treatment with:

  • Antibiotic medicine. This is medicine that kills infections caused by bacteria.
  • Blood transfusions. This means your baby gets new blood put into her body.
  • Pain medicines
  • Oxygen and medicines that help open up blood flow and improve breathing

Anemia. This condition happens when your baby doesn’t have enough healthy red blood cells to carry oxygen to the rest of his body. Signs and symptoms include:

  • Being pale
  • Tiring easily
  • Breathing problems
  • Slower growth and later puberty than healthy children

Treatment depends on your child’s symptoms and may include antibiotics and blood transfusion.

Hand-foot syndrome. This condition happens when the sickle cells block blood flow in your child’s hands and feet. Signs and symptoms include fever and pain, swelling or coldness in the hands and feet. Your baby’s provider may recommend pain medicine and fluids to treat hand-foot syndrome.

Infections, including pneumonia (lung infection) and meningitis (infection of the lining of the brain). Signs and symptoms may include:

  • Fever
  • Coughing
  • Breathing problems
  • Pain in the bones
  • Headaches

You can help protect your child from certain infections by making sure she’s up to date on her vaccinations. If your baby does get an infection, treatment usually is with antibiotic medicine. And taking regular regular antibiotic medicine helps prevent her from getting infections between 2 months and 5 years of age.

Pain episodes. These are common and happen when sickle cells block blood flow. Pain can occur in organs and joints. It can last a few hours, a few days or even for weeks. For some children, pain episodes can happen up to six or more times a year. To help prevent pain episodes in your child, make sure she:

  • Drinks plenty of fluids
  • Doesn’t get too hot or cold
  • Stays away from places with high altitudes where oxygen levels are low
  • Avoids exercise or activities that make her feel very tired

Treatment for pain episodes includes:

  • Heating pads
  • Over-the-counter pain relievers or fever reducers, like acetaminophen and ibuprofen. Over-the-counter means you can buy these without a prescription from your health care provider.
  • Prescription pain medicines. You need a prescription from your baby’s provider for these medicines. A prescription is an order for medicine written by a health care provider.
  • Hydroxyurea. This is a medicine that helps the body make a kind of hemoglobin (called fetal hemoglobin) that a baby makes before birth. The medicine may prevent red blood cells from sickling.

Splenic crisis. This condition happens when the spleen gets clogged with sickle cells and swells up. The spleen is an organ that filters blood in your body and fights infection. Signs and symptoms include pain on the left side of the belly, weakness and a rapid heart rate. Splenic crisis usually is treated in the hospital with blood transfusions. Your child’s provider may recommend removing the spleen if your child has splenic crisis often.

Stroke. This condition can happen when sickle cells block blood flow to the brain. Signs and symptoms include severe headache, weakness on one side of the body, and changes in alertness, speech, vision or hearing. If your child has any of these signs or symptoms, contact your health provider right away for treatment. His provider may recommend using a special kind of ultrasound, called Doppler ultrasound, on the brain to find out your child’s risk for stroke. She may recommend a yearly ultrasound starting at age 2.

Vision problems. Vision problems and blindness can happen when sickle cells block blood flow in your child’s eyes or in the part of the brain that the eyes connect to. His provider may recommend regular eye exams. Laser treatment of the eyes may prevent further vision loss.

Is there a cure for SCD?
There is no widely available cure for SCD. But a small number of children with SCD have been cured through stem cell transplant.

Stem cells are cells that can develop into many different kinds of cells in the body. They serve as a repair system for the body. Stem cells are found in bone marrow. This is the spongy tissue inside some bones, like your hip and thigh bones. Stem cells also are found in umbilical cord blood, the blood in the umbilical cord and placenta. This blood can be collected after the umbilical cord is cut at birth. Talk to your health care provider if you’re thinking about collecting your baby’s umbilical cord blood.

In a stem cell transplant for SCD, stem cells taken from a healthy person are put into a person with SCD. This procedure is very risky and can have serious side effects, including death. Talk to your child’s health care provider to find out more about stem cell transplant for SCD.

For more information
Centers for Disease Control and Prevention (CDC)
National Heart, Lung and Blood Institute
Sickle Cell Disease Association of America

Last reviewed November 2012

See also: Genetic counseling

Spina bifida

Spina bifida is a birth defect that affects the lower back and, sometimes, the spinal cord. It is one of the most common birth defects in the United States, affecting about 1,500 babies each year (1).

Spina bifida is the most common of a group of birth defects called neural tube defects (NTDs). The neural tube is the embryonic structure that develops into the brain and spinal cord. The neural tube normally folds inward and closes by the 28th day after conception. When it fails to close completely, defects of the spinal cord and vertebrae (small bones of the spine) can result.

How does spina bifida affect a child?
There are three forms of spina bifida:

  1. Occulta: In this mildest form, there are usually no symptoms. Affected individuals have a small defect or gap in one or more of the vertebrae of the spine. A few have a dimple, hairy patch, dark spot or swelling over the affected area. The spinal cord and nerves usually are normal, and most affected individuals need no treatment.
  2. Meningocele: In this rarest form, a cyst or fluid-filled sac pokes through the open part of the spine. The sac contains the membranes that protect the spinal cord, but not the spinal nerves. The cyst is removed by surgery, usually allowing for normal development.
  3. Myelomeningocele: In this most severe form, the cyst holds both the membranes and nerve roots of the spinal cord and, often, the cord itself. Or there may be a fully exposed section of the spinal cord and nerves without a cyst. Affected babies are at high risk of infection until the back is closed surgically, although antibiotic treatment may offer temporary protection. In spite of surgery, affected babies have some degree of leg paralysis and bladder- and bowel-control problems. In general, the higher the cyst on the back, the more severe the paralysis.

What causes spina bifida?
The causes of spina bifida are not completely understood. Scientists believe that both genetic and environmental factors act together to cause this and other NTDs. However, 95 percent of babies with spina bifida and other NTDs are born to parents with no family history of these disorders (2).

Who is at risk of having a baby with spina bifida?
Anyone can have a baby with spina bifida. However, couples who have already had a baby with spina bifida or another NTD have an increased risk of having another affected baby. A couple with one child with spina bifida usually has about a 4 percent chance of having another affected baby, and a couple with two affected children has about a 10 percent chance of having another affected baby (2). Similarly, when one parent has spina bifida, there is about a 4 percent chance of passing the disorder on to the baby (2). Couples who have had an affected baby or have a family history of NTDs should consult a genetic counselor to discuss risks to their future children.

In most cases, spina bifida occurs by itself. However, sometimes spina bifida occurs as part of a syndrome with other birth defects. In these cases, recurrence risks in another pregnancy may vary widely.

Women with certain health conditions are at increased risk of having a baby with spina bifida. These conditions include (2,3):

  • Obesity
  • Poorly controlled diabetes
  • Treatment with certain anti-seizure medications

Women with these conditions should consult their health care provider before pregnancy about steps they can take to reduce their risk of having a baby with spina bifida. For example, they can achieve a healthy weight before pregnancy, control their diabetes, change anti-seizure medications and take folic acid (see below).

Spina bifida and other NTDs occur more commonly in some ethnic groups than others. For example, NTDs are more common in Hispanics and Caucasians, and less common among Ashkenazi Jews, most Asian ethnic groups and African-Americans (2).

How is spina bifida treated?

  • Occulta: This condition usually requires no treatment. Most individuals don’t know they are affected, unless the defect is diagnosed during an X-ray for some other reason. Occasionally newborns are diagnosed with this form of spina bifida if they have a dimple or other marking on their back. In some cases, these babies may need to be evaluated for spinal cord abnormalities that could eventually result in complications, such as weakness or numbness in the legs and bladder problems. Occasionally surgery is recommended to prevent these problems.
  • Meningocele: This defect is repaired surgically, and affected babies usually have no paralysis.
  • Myelomeningocele: This form of spina bifida usually requires surgery within 24 to 48 hours after birth (2). Doctors surgically tuck the exposed nerves and spinal cord back inside the spinal canal and cover them with muscle and skin. Prompt surgery helps prevent additional nerve damage and infection. However, nerve damage that already has occurred cannot be reversed. Soon after surgery, a physical therapist teaches parents how to exercise their baby’s legs and feet to prepare for walking with leg braces and crutches. Many children with a defect in the lower spine can walk with or without these devices, although most children with a defect high in the spine require a wheelchair.

What medical problems occur with spina bifida?
Common medical problems include:

  • Hydrocephalus: About 70 to 90 percent of children with myelomeningocele develop hydrocephalus, a build-up of fluid in and around the brain(4). Cerebrospinal fluid cushions and protects the brain and spinal cord. When the fluid is unable to circulate normally, it collects in and around the brain, causing the head to be enlarged. Without treatment, hydrocephalus can cause brain damage and intellectual disabilities.

    Doctors usually treat hydrocephalus by surgically inserting a tube called a shunt that drains the excess fluid. The shunt runs under the skin into the chest or abdomen, and the fluid passes harmlessly into the child’s body. A newer surgical procedure called endoscopic third ventriculostomy creates a new pathway for draining cerebrospinal fluid. This procedure may be recommended for some children older than 6 months, including some who experience shunt malfunctions(5).
  • Chiari II malformation: Nearly all children with myelomeningocele have an abnormal change in the position of the brain. The lower part of the brain is located farther down than normal and is partly displaced into the upper part of the spinal canal. This can block the flow of cerebrospinal fluid and contribute to hydrocephalus. In most cases, affected children have no other symptoms. But a small number develop serious problems, such as breathing and swallowing difficulties and upper body weakness. In these cases, doctors may recommend surgery to relieve pressure on the brain.
  • Tethered spinal cord: Most children with myelomeningocele, and a small number with meningocele or spina bifida occulta, have a tethered spinal cord. This means that the spinal cord does not slide up and down with movement as it should, because it is held in place by surrounding tissue. Some children have no symptoms, but others develop leg weakness, worsening leg function, scoliosis (curvature of the spine), pain in the back or legs, and changes in bladder function. Doctors usually recommend surgery to release the spinal cord from surrounding tissue. After surgery, a child should return to his usual level of functioning.
  • Urinary tract disorders: Because of nerve damage, individuals with myelomeningocele often have problems emptying the bladder completely. This can lead to urinary tract infections and kidney damage. A technique called intermittent catheterization, in which the parent or child inserts a plastic tube into the bladder several times a day, is often helpful. Children with spina bifida should have regular care by a urologist (a doctor who specializes in urinary tract problems) to help prevent urinary tract problems.
  • Latex allergy: According to the Spina Bifida Association (SBA), many children with myelomeningocele are allergic to latex (natural rubber), possibly due to repeated exposures during surgeries and medical procedures (4). Symptoms include watery eyes, wheezing, hives, rash and even life-threatening breathing problems. Doctors should consider using nonlatex gloves and equipment during procedures on individuals with spina bifida. Affected individuals and their families should avoid latex items often found in the home and community, such as most baby bottle nipples, pacifiers and balloons. A list of safe and unsafe items is available from the Spina Bifida Association.
  • Learning disabilities: At least 80 percent of children with myelomeningocele have normal intelligence (4). However, some have learning problems.
  • Other conditions: Some individuals with myelomeningocele have additional physical and psychological problems, such as obesity, digestive tract disorders, depression and sexual issues.

    With treatment, children with spina bifida usually can become active individuals. Most live normal or near-normal life spans (6).

Can spina bifida be prevented?
A B-vitamin called folic acid can help prevent spina bifida and other NTDs. Studies show that if all women in the United States took the recommended amount of folic acid before and during early pregnancy, up to 70 percent of NTDs could be prevented(1). It is important for a woman to have enough folic acid in her system before pregnancy and during the early weeks of pregnancy, before the neural tube closes.

The March of Dimes recommends that all women of childbearing age take a multivitamin with 400 micrograms of folic acid every day before pregnancy and during early pregnancy. However, a woman should not take more than 1,000 micrograms (or 1 milligram) without her provider’s advice.

Healthy eating includes eating foods that are fortified with folic acid and foods that contain folate, the natural form of folic acid that is found in foods. Many grain products in the United States are fortified with folic acid. This means that a synthetic (manufactured) form of folic acid is added to them. Enriched flour, rice, pasta, bread and cereals are examples of fortified grain products. (A woman can check the label to see if a product is enriched.) Folate-rich foods include leafy green vegetables, beans and orange juice.

Women who already have had a baby with spina bifida or another NTD, as well as women who have spina bifida, diabetes or seizure disorders, should consult their health care provider before another pregnancy about the amount of folic acid to take. Studies have shown that taking a ten-fold larger dose of folic acid daily (4 milligrams), beginning at least 1 month before pregnancy and in the first trimester of pregnancy, reduces the risk of having another affected pregnancy by about 70 percent (2,7).

Can spina bifida be detected prenatally?
Health care providers routinely offer pregnant women screening tests to help identify fetuses at increased risk of spina bifida. These screening tests include a blood test called the quad screen and an ultrasound. The blood test measures the levels of four substances in the mother’s blood to identify pregnancies at higher-than-average risk of spina bifida and other NTDs, as well as Down syndrome and certain related birth defects.

If the screening test suggests an increased risk of spina bifida, the health care provider may recommend additional tests that are accurate in detecting severe spina bifida. The tests are a detailed ultrasound of the fetal spine and amniocentesis. A detailed ultrasound can help determine the seriousness of spina bifida and whether certain complications are present. In amniocentesis, the doctor inserts a needle into the woman’s uterus to take a small sample of amniotic fluid. The fluid is sent to a lab to measure levels of alpha-fetoprotein (AFP) in the fluid. An abnormal amount of the protein in the fluid is associated with spina bifida.

What are the benefits of detecting spina bifida before birth?
When spina bifida is diagnosed early in pregnancy, women can consult with their health care provider to learn more about the disorder and to consider their options. For example, they can plan for delivery in a specially equipped medical center so that the baby can have any necessary surgery or treatment soon after birth.

Parents and doctors also can discuss whether a vaginal or cesarean delivery would be best for their baby. Fetuses with myelomeningocele are more likely than other babies to be in a breech (feet-first) position. A cesarean delivery is generally recommended for these babies (2). Some doctors may recommend a cesarean delivery for babies with myelomeningocle who are in a normal head-first position, especially if they have a large cyst (3,8). One study found that a planned cesarean delivery can reduce the severity of paralysis in babies with myelomeningocele; however, several studies found no reduction in paralysis in babies delivered by cesarean (2,8,9).

More than 400 babies have undergone experimental prenatal surgery to repair myelomeningocele before birth( 10). This approach is based on the idea that early repair (between the 19th and 25th weeks of pregnancy) may help prevent damage to exposed spinal nerve tissue in the womb and reduce paralysis and other complications. Preliminary results suggest that children who have prenatal surgery have improvements in the Chiari malformation and may need a hydrocephalus shunt less frequently, but their bladder and bowel function do not appear to be improved (2,3). One study found better-than-expected walking ability in toddlers, but other studies did not (3,11). This procedure poses surgery-related risks to mother and baby and puts the baby at high risk of premature delivery (before 37 completed weeks of pregnancy). Prematurity increases the risk of health problems during the newborn period and lasting disabilities. Doctors do not yet know whether the benefits of prenatal surgery outweigh these risks.

To find out whether prenatal or postnatal surgery is more effective, the National Institute of Child Health and Human Development (NICHD), a part of the National Institutes of Health (NIH), is conducting a study to compare the results of both types of surgery in 200 babies with myelomeningocele( 6). Half of the babies undergo surgery before birth, while the other half have surgery shortly after birth. The surgery is being carried out at three major medical centers: Children’s Hospital of Philadelphia, the University of California at San Francisco and Vanderbilt University Medical Center in Nashville. More about this research is available at the study Web site or (866)-ASK-MOMS (866-275-6667).

Is the March of Dimes conducting research on spina bifida?
Several March of Dimes grantees are searching for genes that may contribute to spina bifida and other NTDs to develop new ways to prevent these disorders. Others are seeking a better understanding of how folic acid prevents NTDs, to make this treatment even more effective.

The March of Dimes is a member of the National Council on Folic Acid, an alliance of organizations working to promote the benefits and consumption of folic acid.

Where can families find additional information on spina bifida?
More information is available from:

References

  1. Centers for Disease Control and Prevention (CDC). Spina Bifida. Created 3/11/09.
  2. American College of Obstetricians and Gynecologists (ACOG). Neural Tube Defects. ACOG Practice Bulletin, number 44, July 2003 (reaffirmed 2008).
  3. Fichter, M.A., et al. Fetal Spina Bifida Repair – Current Trends and Prospects of Intrauterine Neurosurgery. Fetal Diagnosis and Therapy, 2008, volume 23, pages 271-286. \
  4. Spina Bifida Association. About Spina Bifida, accessed 6/12/09.
  5. Jallo, G.I., et al. Endoscopic Third Ventriculostomy. Neurosurg Focus, volume 19, number 6, E11, December 2005.
  6. Management of Myelomeningocele Study. About Spina Bifida, accessed 6/9/09.
  7. Centers for Disease Control and Prevention (CDC). Folic Acid. Updated 3/31/09.
  8. Hamrick, S.E.G. Cesarean Delivery and Its Impact on the Anomalous Infant. Clinics in Perinatology, volume 35, 2008, pages 395-406.
  9. Luthy, D.A., et al. Cesarean Section Before the Onset of Labor and Subsequent Motor Function in Infants with Meningomyelocele Diagnosed Antenatally. New England Journal of Medicine, volume 324, 1991, pages 662-666.
  10. Sutton, L.N. Fetal Surgery for Neural Tube Defects. Best Pract Res Clin Obstet Gynaecol, February 2008, volume 22, number 1, pages 175-188.
  11. Danzer, E., et al. Lower Extremity Neuromotor Function and Short-Term Ambulatory Potential Following In Utero Myelomeningocele Surgery. Fetal Diagnosis and Therapy, 2009, volume 25, pages 47-53.

August 2009

Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are inherited diseases of the central nervous system. These diseases have the same symptoms, though they are caused by mutations (changes) in different genes. A severe form of each disease can affect babies and is fatal.

What are the symptoms of Tay-Sachs and Sandhoff diseases?
Babies with the classic (infantile) forms of Tay-Sachs and Sandhoff diseases appear healthy at birth and seem to develop normally for the first few months of life. Symptoms generally appear by about 6 months of age when the baby gradually stops smiling, crawling, turning over and reaching out. The baby continues to lose skills gradually and eventually becomes blind, paralyzed and unaware of surroundings. Babies with Tay-Sachs disease usually die by age 4; those with Sandhoff disease, by age 3 (National Institute of Neurological Disorders and Stroke (NINDS), 2007; NINDS, 2009; Online Mendelian Inheritance in Man #268800, 2009).

What causes the symptoms of these diseases?
Babies with classic Tay-Sachs and Sandhoff diseases lack an enzyme (protein) called hexosaminidase. There are two versions of this enzyme, hex A and hex B. Babies with Tay-Sachs disease do not make hex A, and babies with Sandhoff disease do not make either hex A or hex B. A small number of babies with Tay-Sachs disease (AB variant) make both versions of the enzyme but lack another protein that is needed for these enzymes to work properly.

Hexosaminidase is necessary for breaking down certain fatty substances (called GM2 gangliosides) in cells of the brain. Without this enzyme, these fatty substances build up and gradually destroy brain cells, until the entire central nervous system stops working.

Are there other forms of Tay-Sachs and Sandhoff diseases besides the classic type that affects babies?
There are late-onset forms of these diseases, with symptoms developing in childhood or adulthood. While babies with the classic forms of these diseases do not produce any enzyme, individuals with the late-onset forms produce very small amounts. This is probably why their symptoms begin later in life and generally are milder than in the classic form.

There are three late-onset forms of Tay-Sachs disease:

  • Juvenile (subacute): Symptoms begin between 2 and 10 years of age and resemble those of the classic form (Kaback, 2006; Online Mendelian Inheritance in Man, #272800, 2009). Although the course of the disease is slower, death generally occurs by age 15 (Online Mendelian Inheritance in Man, #272800, 2009; Maegawa, 2006).

  • Chronic: Symptoms begin by age 10 and progress slowly (Kaback, 2006). Symptoms vary and may include poor coordination, unsteady gait, muscle cramps, slurred speech and, sometimes, mental illness. Cognitive abilities may not be affected or may be affected late in the course of the disease (Kaback, 2006). Life expectancy varies (Chicago Center for Jewish Genetic Disorders, 2007).

  • Adult-onset: This is the mildest form with symptoms developing in adolescence or adulthood. Symptoms vary greatly in severity and can include slurred speech, muscle weakness, muscle cramps, tremors, unsteady gait and, sometimes, mental illness (Kaback, 2006; National Tay-Sachs and Allied Diseases Association, Inc., 2009). Affected individuals usually do not lose vision or hearing. Some individuals may have loss of certain mental abilities, including problems with memory. Life expectancy varies and, in some cases, appears to be unaffected (Kaback, 2006; National Tay-Sachs and Allied Diseases Association, Inc., 2009).

Late-onset forms of Sandhoff disease are rare and appear to share many of these symptoms.

Is there any treatment for these diseases?
There is currently no treatment to prevent these diseases from running their course. Affected individuals can be made as comfortable as possible and given other supportive care.

Researchers are investigating whether stem cell transplants could help babies with classic Tay-Sachs and Sandhoff diseases. Stem cells are immature blood cells that produce all other kinds of blood cells. Stem cells are obtained from umbilical cord blood or from the bone marrow of a donor. Unfortunately, stem cell transplantation has not yet been successful in stopping or reversing brain damage in Tay-Sachs or Sandhoff diseases, and this treatment poses a high risk of death in affected babies (NINDS, 2007; NINDS, 2009).

Researchers also are studying the effectiveness of drug treatments (including a drug called miglustat, which is approved by the Food and Drug Administration to treat a related disorder) to help reduce the build-up of fatty substances in brain cells in individuals with these diseases (National Tay-Sachs and Allied Diseases Association, Inc., 2009).

Who is at risk for Tay-Sachs and Sandhoff diseases?
Tay-Sachs disease occurs most frequently in descendants of Central and Eastern European (Ashkenazi) Jews. About 1 out of every 30 American Jews carries a mutation in the gene that codes for hex A (Kaback, 2006; American College of Obstetricians and Gynecologists (ACOG), 2005). Some non-Jewish individuals of French-Canadian ancestry (from the St. Lawrence River Valley of Quebec) and members of the non-Jewish Cajun population in Louisiana and the Old Order Amish in Pennsylvania also are at increased risk (Kaback, 2006; American College of Obstetricians and Gynecologists (ACOG), 2005). Individuals in other ethnic groups in this country have about a 1 in 300 chance of carrying a mutation in this gene (Kaback, 2006; American College of Obstetricians and Gynecologists (ACOG), 2005).

Sandhoff disease can occur in any ethnic group, though it is uncommon. Individuals not of Jewish ancestry are more likely than those of Jewish ancestry (1 in 600 vs. 1 in 1,000) to carry one of the gene mutations that cause Sandhoff disease (Online Mendelian Inheritance in Man #268800, 2009).

How are the diseases transmitted?
All forms of Tay-Sachs and Sandhoff diseases are inherited. Tay-Sachs disease is caused by mutations in a gene on chromosome 15 that codes for hex A. Sandhoff disease is caused by mutations in a gene on chromosome 5 that codes for hex B. Both diseases are passed on through parents who carry one of these mutations. A carrier does not have the illness. However, when two carriers become parents:

  • There is a 25-percent (1 in 4) chance that any child they have will inherit a gene mutation from each parent and have the disease.
  • There is a 25-percent chance (1 in 4) that the child will inherit the normal gene from each parent. The child will not have the disease and will not be a carrier.
  • There is a 50-percent (2 in 4) chance that the child will inherit one normal and one abnormal gene. The child will not have the disease but will be a carrier like the parents.

If only one parent is a carrier, the couple’s children cannot inherit the disease. However, each child has a 50-percent chance of inheriting the gene mutation and being a carrier.

Carrier screening is commonly performed before or during pregnancy for adults in populations who are at risk for these disorders.

How can people find out if they are carriers?
An individual can take a test that measures the amount of hexosaminidase in the blood. Tay-Sachs carriers have about half as much of hex A as noncarriers, but this is plenty for the carrier’s own needs. Similarly, carriers of Sandhoff disease have reduced but adequate amounts of both hex A and hex B.

A blood sample can be used to perform DNA-based genetic testing for known mutations in the hex A and hex B genes. Genetic testing may be recommended if the results of the carrier screening test are uncertain.

Carrier screening is available from a genetic services center or clinic. A health care provider can provide referrals to local sites where testing is available, as can the National Tay-Sachs and Allied Diseases Association.Trained genetic counselors explain test results so that individuals know whether or not their children are at risk for the disease.

Can these diseases be diagnosed before birth?
Yes. Prenatal tests called chorionic villus sampling (CVS) and amniocentesis can diagnose these diseases before birth. These tests are available when both members of a couple are carriers or when one is a carrier and the other has uncertain or unknown carrier status.

CVS generally is done between 10 and 12 weeks of pregnancy. In CVS, the doctor retrieves a sample of cells from the developing placenta either through a thin tube inserted through the vagina or by inserting a needle through the mother’s abdomen. The placenta contains cells that are genetically identical to those of the fetus, and these cells are examined for the presence of hex A (when testing for Tay-Sachs) or hex A and hex B (when testing for Sandhoff). The lab can test for gene mutations in addition to the enzyme.

Amniocentesis usually is done between 15 and 20 weeks of pregnancy. In this test, the doctor inserts a needle into the mother’s abdomen to take a sample of fluid that surrounds the fetus. The fluid contains fetal cells, which are tested for the presence of the enzyme and/or gene mutations.

Some medical centers offer genetic testing to carrier couples who undergo in vitro fertilization (a process in which eggs are removed from a woman’s ovaries and fertilized in the laboratory with her partner’s sperm). The embryos are tested for a genetic disease, and only healthy ones are implanted in the mother. This is called preimplantation genetic testing.

Couples who are carriers of a Tay-Sachs or Sandhoff gene or those who may be at increased risk due to ethnic background or family history may want to consult a genetic counselor. These health professionals help families understand what is known about the causes of a birth defect and the chances of the birth defect occurring in a pregnancy. They also help guide families through the testing process. Genetic counselors can provide referrals to medical experts and appropriate support groups in the community. Genetic counseling is available at most large medical centers and teaching hospitals. To find a genetic counselor in their area, individuals can ask their health care provider or contact the National Society of Genetic Counselors.

Does the March of Dimes support research on Tay-Sachs and Sandhoff diseases?
Yes. March of Dimes grantees helped pinpoint mutations in the hex A gene that are responsible for late-onset forms of Tay-Sachs disease. Information about specific mutations leads to improved diagnosis and carrier screening for all forms of Tay-Sachs disease.

Current grantees are attempting to develop drug treatments that may prevent the production of certain fatty substances that build up and impair brain cells in individuals with Tay-Sachs and Sandhoff diseases. This approach eventually may help prevent the loss of central nervous system function and early deaths associated with these diseases.

For more information

References

  1. American College of Obstetricians and Gynecologists (ACOG). (2005). Screening for Tay-Sachs disease. (ACOG Committee Opinion, volume 318, reaffirmed 2007).
  2. Chicago Center for Jewish Genetic Disorders. (2007). Tay-Sachs disease. Retrieved September 7, 2007 from: jewishgenetics.org/?q=content/tay-sachs-disease.
  3. Kaback, M.M. (2006). Hexosaminidase A deficiency. GeneReviews. Retrieved June 23, 2009 from: ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tay-sachs.
  4. Maegawa, G.H.B. (2006). The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported. Pediatrics, 118, e1550-e1562.
  5. National Institute of Neurological Disorders and Stroke (NINDS). (2009). NINDS Sandhoff disease information page. Retrieved April 19, 2009 from: ninds.nih.gov/disorders/sandhoff/sandhoff.htm.
  6. National Institute of Neurological Disorders and Stroke (NINDS). (2007). NINDS Tay-Sachs disease information page. Retrieved December 2, 2009 from: ninds.nih.gov/disorders/taysachs/taysachs.htm.
  7. National Tay-Sachs and Allied Diseases Association, Inc.(2009). What is Tay-Sachs disease? Retrieved June 23, 2009 from: ntsad.org.
  8. Online Mendelian Inheritance in Man. (2009). Sandhoff disease #268800. Retrieved April 10, 2009 from: ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=268800.
  9. Online Mendelian Inheritance in Man. (2009). Tay-Sachs disease #272800. Retrieved March 5, 2009 from: ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=272800/.

December 2009

Thalassemia

Thalassemia is a general name for a group of inherited blood diseases that involve abnormalities in hemoglobin, the oxygen-carrying part of the red blood cells. Hemoglobin is mainly made up of two kinds of protein, called alpha and beta globin. Individuals with thalassemia do not produce enough of one (or occasionally both) of these proteins. As a result, their red blood cells may be abnormal and unable to carry enough oxygen throughout the body.

The two main types of thalassemia are called alpha and beta thalassemia:

  • Individuals with alpha thalassemia do not produce enough alpha globin.
  • Those with beta thalassemia do not produce enough beta globin.

There are a number of different forms of alpha and beta thalassemias, with symptoms ranging from mild to severe.

Thalassemia is among the most common genetic disorders worldwide (1). More than 100,000 babies worldwide are born each year with severe forms of thalassemia (2). Thalassemia occurs most frequently in people of Italian, Greek, Middle Eastern, Asian and African ancestry (3).

What is alpha thalassemia?
There are at least five main types of alpha thalassemia. These are most common in people of Southeast Asian, Indian, southern Chinese, Middle Eastern and African ancestry (4). There are four genes that control the production of alpha globin. The severity of the condition is determined by how many of these genes are missing or abnormal.

  • Silent carrier, the mildest form, has one alpha globin gene missing or abnormal. Affected individuals generally have no symptoms, but they can pass on the genetic abnormality to their children.
  • Alpha thalassemia minor (also called alpha thalassemia trait) has two missing or abnormal alpha globin genes. Affected individuals may have no symptoms or a mild anemia, but they can pass the condition on to their children.
  • Hemoglobin H disease is caused by three missing or abnormal alpha globin genes (so there is one normal alpha globin gene). The condition causes abnormalities in red blood cells and rapid destruction of these cells. Most affected individuals have mild to moderate anemia and can live fairly normal lives. The anemia may temporarily worsen when individuals have a viral infection or when they are treated with certain medications (such as sulfa drugs) (5).

    Some affected individuals eventually develop complications, such as an enlarged spleen or gallstones (5). Individuals with hemoglobin H disease should receive regular medical care to detect and treat these complications. Some may need occasional blood transfusions (6).
  • Hemoglobin H-Constant Spring is a more severe form of hemoglobin H disease. Affected individuals have one normal alpha globin gene, plus a specific mutation (change) called Constant Spring on one of their three abnormal genes. People with this condition generally have moderate to severe anemia and often develop complications, such as an enlarged spleen. Some need blood transfusions from time to time, such as when they develop an illness with a fever, while others need more frequent transfusions (5, 6).
  • Alpha thalassemia major, the most severe form, is caused when there are no alpha globin genes. Affected fetuses suffer from severe anemia, heart failure and fluid buildup. They usually are stillborn, but some die in the first hours after birth. In rare cases, babies diagnosed and treated before birth with blood transfusions have survived. These babies require lifelong blood transfusions (4, 5).

What is beta thalassemia?
There are three main forms of beta thalassemia. These are most likely to affect people of Greek, Italian, Middle Eastern, Southeast Asian, southern Chinese and African descent (4). Two genes control the production of beta globin. Mutations on one or both of them can cause the disorder. The severity of the condition is determined by whether one or both beta globin genes carry a mutation and by the severity of the mutation.

  • Thalassemia minor (also called thalassemia trait) is caused by a mutation on one beta globin gene. Most affected individuals have no symptoms, though some have mild anemia. Affected individuals can pass the abnormal gene on to their offspring.
  • Thalassemia intermedia results from abnormalities in both beta globin genes. These gene abnormalities are generally less severe than those that cause thalassemia major. Affected children usually have mild to moderate anemia, and they may develop some of the complications seen in thalassemia major, including enlarged spleen and bone abnormalities. Many affected individuals require occasional or more frequent blood transfusions to reduce complications (1).
  • Thalassemia major, the most severe form, results from severe mutations on both beta globin genes. It also is called Cooley's anemia, named after the doctor who first described it in 1925. Most affected children appear healthy at birth. However, during the first year or two of life, they become pale and fussy and have a poor appetite. They grow slowly and often develop jaundice (yellowing of the eyes and skin). Without treatment, they develop an enlarged spleen and liver, thinning bones that break easily, abnormal facial bones, frequent infections and heart problems, and they die in the first decade of life. Affected children require regular blood transfusions beginning in infancy.

Other forms of thalassemia include:

  • E-beta thalassemia results from one beta globin gene carrying a thalassemia mutation (thalassemia minor) and one beta globin gene carrying a mutation that produces a variant form of hemoglobin called hemoglobin E. This condition is most common in people from Southeast Asia, including Cambodia, Vietnam and Thailand (4). Individuals who produce hemoglobin E generally are healthy or have only a mild anemia. However, those with E-beta thalassemia have mild to severe anemia, resembling beta thalassemia intermedia or beta thalassemia major (4).
  • Hb S/beta thalassemia results from one beta globin gene carrying a thalassemia mutation (thalassemia minor) and one gene for sickle cell disease, another inherited anemia. It is most common in those of African or Mediterranean ancestry (4). Symptoms generally resemble those of sickle cell disease, including varying degrees of anemia, serious infections, pain and damage to vital organs.

What is the treatment for thalassemia?
Blood transfusions are used to treat severe forms of thalassemia. Children and adults with beta thalassemia major require regular transfusions. Some individuals with beta thalassemia intermedia, E-beta thalassemia and hemoglobin H-Constant Spring require transfusions from time to time, or sometimes more frequently. Some may need a transfusion if they develop a viral illness or other infection, which may cause anemia to become more severe. Health care providers may recommend more frequent transfusions if these individuals develop complications.

Children with severe thalassemia, such as beta thalassemia major, generally receive a transfusion every two to three weeks (4). Regular transfusions help keep hemoglobin levels near normal and help prevent many of the complications of thalassemia. This treatment improves the child's growth and well-being and usually prevents heart failure and bone deformities.

Unfortunately, repeated blood transfusions lead to a buildup of iron in the body. Iron buildup can damage the heart, liver and other organs. To help prevent organ damage, children and adults who receive regular transfusions are treated with a type of drug called an iron chelator. This drug binds to iron and helps the body get rid of excess iron.

Until recently, the only drug approved in the United States to prevent iron buildup was deferoxamine (Desferal or DFO). Individuals usually receive this drug over 8 to 12 hours, while they are sleeping, five to seven nights a week. A small pump delivers the drug through a needle placed under the skin. In November 2005, the U.S. Food and Drug Administration (FDA) approved the first oral iron chelating drug (Exjade or deferasirox) (7). This tablet is dissolved in water or juice and drunk once a day. Some individuals with severe thalassemia now can choose between these treatments.

Individuals with beta thalassemia major who are treated with regular blood transfusions and iron chelation often live 40 years or longer (2). The most common cause of death in these individuals is heart complications caused by iron buildup (8).

Children and adults with thalassemia must undergo tests to measure the level of iron in their bodies. Blood tests are used to measure the amount of iron in the blood. Unfortunately, blood tests are not very accurate in measuring the levels of iron in the heart and liver. Providers may recommend a yearly liver biopsy, a surgical procedure in which a small amount of liver tissue is removed and tested. A few medical centers have begun to use new, noninvasive imaging tests called SQUID and T2* to measure iron levels in the liver and heart (1, 2, 4). For more information on where these tests are available, contact the Cooley’s Anemia Foundation at info@cooleysanemia.org.

Is there a cure for thalassemia?
Some children with thalassemia can be cured with a bone marrow transplant. However, this form of treatment is most successful when a donor who is an exact genetic match is available. Generally, a sibling or other family member is most likely to be an exact match. The procedure can cure about 85 percent of children who have a fully matched family donor 9(). However, only about 30 percent of children with thalassemia have a family member who is a suitable donor (4). The procedure is risky and can result in death.

Recent studies suggest that using umbilical cord blood from a newborn sibling may be as effective as a bone marrow transplant (9). Like bone marrow, cord blood contains unspecialized cells called stem cells that produce all other blood cell.

How is the disease transmitted?
All forms of thalassemia are inherited. The disease can not be caught from another person who has it. Thalassemia is passed on through parents who carry abnormal thalassemia genes in their cells.

When both parents carry alpha thalassemia genes, any child they have is at risk for inheriting a more severe form of this condition. Individuals who know they have one of these disorders, those with family histories of these disorders, and those from countries where they are common should consider consulting a genetic counselor to find out whether their children could be at risk. (Health care providers can provide referrals to genetic counselors, or individuals can find them by contacting a major medical center.)

When two individuals with beta thalassemia minor (carriers who each have a mutation on one beta globin gene) have children together, there is a 25 percent chance (1 in 4) that any child they have will inherit a thalassemia gene from each parent and have a severe form of the disease. There is:

  • A 50 percent (2 in 4) chance that the child will inherit one of each kind of gene and have beta thalassemia minor like his parents
  • A 25 percent (1 in 4) chance that the child will inherit two normal genes and be completely free of the disease.

The odds are the same for each pregnancy when both parents have the beta thalassemia minor.

Is there a test for thalassemia?
Yes. Blood tests and family genetic studies can show whether an individual has any form of thalassemia. Newborn screening tests now identify many babies with thalassemia. In addition, prenatal testing using chorionic villus sampling (CVS) or amniocentesis can detect or rule out thalassemia in the fetus.

Can women with thalassemia have healthy pregnancies?
Women with milder forms of thalassemia usually have healthy pregnancies. Until recently, pregnancy was rare in women with beta thalassemia major. Several recent studies suggest that pregnancy appears safe for a woman with well-treated beta thalassemia major who does not have heart problems 9(10). Chelating drugs are usually stopped during pregnancy because it is not known whether they pose risks to the baby (4, 10). As long as a woman’s partner does not carry a gene for beta thalassemia, her children will not be at risk for thalassemia#although all will be carriers (beta thalassemia minor).

What research on thalassemia is being done?
Scientists are working on better ways to remove excess iron from the body to prevent or delay iron overload. They are developing and testing new oral iron-chelating drugs and looking at whether combining one of these drugs with deferoxamine may be more effective than either treatment alone (1, 2).

Researchers are studying the effectiveness of certain drugs (including hydroxyurea, a drug used to treat sickle cell disease) in reactivating the genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth. After birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of individuals with beta thalassemia produce more fetal hemoglobin to make up for their deficiency of adult hemoglobin. Studies to date suggest that treatment with these drugs may be helpful for some patients with beta thalassemia intermedia (2).

Researchers also are exploring the possibility that dietary treatments, such as with vitamin E, may help reduce organ damage from iron buildup (1, 6). Others continue to improve bone marrow transplantation methods that may offer a cure to more children with thalassemia.

March of Dimes grantees have been among the many scientists seeking to develop an effective form of gene therapy that may offer a cure for thalassemia. Gene therapy may involve inserting a normal alpha or beta globin gene into the patient’s stem cells, possibly allowing these immature blood cells to produce normal red blood cells.

For more information:

References

  1. Rund, D. and Rachmilewitz, E. Medical Progress: Beta-Thalassemia. New England Journal of Medicine, volume 353, number 11, September 15, 2005, pages 1135-1146.
  2. New York Academy of Sciences. Cooley’s Anemia Eighth Symposium. Posted 7/22/05, accessed 5/2/08.
  3. National Heart, Lung and Blood Institute. Thalassemias. Posted 1/08.
  4. Cooley’s Anemia Foundation. About Thalassemia. Updated 2007.
  5. Northern California Comprehensive Thalassemia Center. Alpha Thalassemia. Accessed 5/2/08.
  6. Cohen, A.R., et al. Thalassemia. Hematology 2004, American Society of Hematology, pages 14-34.
  7. Food and Drug Administration (FDA). FDA Approves First Oral Drug for Chronic Iron Overload. FDA News, November 9, 2005.
  8. Cunningham, M.J. Update on Thalassemia: Clinical Care and Complications. Pediatric Clinics of North America, volume 55, April 2008, pages 447-460.
  9. Di Bartolomeo, P., et al. Long-term Results of Survival in Patients with Thalassemia Major Treated with Bone Marrow Transplantation. American Journal of Hematology, February 13, 2008 (Epub ahead of print).
  10. American College of Obstetricians and Gynecologists (ACOG). Hemoglobinopathies in Pregnancy. ACOG Practice Bulletin, number 78, January 2007.
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June 2008

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