Gene Linked to Cleft Lip and Palate Identified

Study Published Today in The New England Journal of Medicine

WHITE PLAINS, N.Y. - AUGUST 19, 2004 -- An international team of researchers has identified a gene variant that is a major contributor to oral clefts and triples the risk of recurrence in affected families, it was reported today in The New England Journal of Medicine.

"Cleft lip and cleft palate are among the most common birth defects in the United States," says Nancy S. Green, M.D., medical director of the March of Dimes, which helped fund the study. "This new finding brings us closer to understanding the multiple genetic factors underlying these very serious birth defects, with probable environmental effects."

The discovery also has important implications for genetic counseling for families who have had one or more children with an isolated cleft lip and/or cleft palate (not associated with any syndrome or other malformation), Dr. Green says.

"A special strength of this study is that its findings come from a variety of ethnic groups, including Europeans, South Americans, and Asians," Dr. Green says.  "This gives us confidence that the linkage of this gene variant to oral clefts is true across different populations in the U.S. and worldwide."

The March of Dimes provided funding to Eduardo E. Castilla, M.D., Ph.D., Professor at ECLAMC, a  genetic resource facility in Brazil, as well as to a collaboration between Andrew Lidral, D.D.S., Ph.D., Associate Professor, Department of Orthodontics, University of Iowa, Iowa City, and Mauricio Arcos-Burgos, M.D., Ph.D., at the University of Antioquia, Medellin, Colombia.

Cleft lip (with and without cleft palate) occurs in about 1 in every 1,000 births in the U.S., or more than 4,000 babies each year.  A cleft is an opening or separation in a body structure.  Clefts that occur in the oral-facial region often involve the upper lip, the roof of the mouth (hard palate), or the soft tissue in the back of the mouth (soft palate).  More than 70 percent of babies with cleft lip also have cleft palate.  Children with oral clefts experience difficulties in chewing, swallowing, and speaking, and are prone to frequent ear infections that can lead to hearing loss.  Depending on the severity of the cleft, dental problems may also occur.  Surgical repair is an important part of treatment for oral clefts, but is not a complete solution for many children. 

Isolated clefts are associated with an overall lifetime increase in the risk of premature death from all causes, according to a recent long-term followup study. 

"Interferon Regulatory Factor 6 (IRF6) Gene Variants and the Risk of Isolated Cleft Lip or Palate" by Theresa M. Zucchero, B.S., of the University of Iowa and others was published in NEJM, volume 351, number 8, pages 769-80.

An accompanying editorial, "Finding Needles in Haystacks -- IRF6 Gene Variants in Isolated Cleft Lip or Cleft Palate," by Aravinda Chakravarti, Ph.D., of Johns Hopkins University School of Medicine, appeared in NEJM on pages 822-824.