Gene variant that is a major contributor to cleft lip

Aug 18 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.

Worldwide about 1 of every 700 people is born with a cleft lip, either with or without a cleft palate. Asians and American Indians are slightly more likely to have the birth defect than Caucasians, while African Americans have a much lower risk. The disfiguring gap or opening in the lip or the roof of the mouth can cause dental and speech problems, trouble eating, and other difficulties. In the United States the problem is usually corrected through multiple surgeries over the course of many years.

Clefts that occur in the oral-facial region often involve the lip, the roof of the mouth or the soft tissue in the back of the mouth. Two major types of oral-facial clefts are cleft lip/palate and isolated cleft palate. Babies with cleft lip/palate have a cleft lip which usually is accompanied by cleft palate. In isolated cleft palate, the cleft palate occurs by itself, without cleft lip or other malformations. These two forms of oral-facial clefts are considered separate birth defects.

"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.

http://www.modimes.org/