According to Murray, roughly one in every 600 babies in the United States is born with the isolated, also called "non-syndromic," cleft lip and palate. Though the condition is usually correctable with several surgeries, families undergo tremendous emotional and economic hardship during the process, and children often require many other services, including complex dental care and speech therapy.
The challenge has been how to move the field forward. Isolated clefts arise during fetal development from a dynamic and still poorly understood interplay of genes, diet, and environmental factors, and current research tools cannot adequately cut through the complexity.
One productive inroad has been to isolate genes linked to "syndromic" cleft lip and palate, hoping some might also play a role in causing the isolated condition. Syndromic cleft lip and palate refers to babies born with clefts that are accompanied with other birth defects. There are over 150 of these syndromes, and, collectively, they account for about 30 percent of all cleft lip and palate.
Two years ago, Murray and colleagues Brian Schutte and Shinji Kondo hit the jackpot when they found the IRF6 gene plays a role in causing Van der Woude syndrome (VWS), the most common of the syndromic conditions. The discovery marked a potentially important lead because, about 15 percent of people with VWS have malformations that are clinically indistinguishable from isolated cleft lip and palate, suggesting the gene might be involved in both types of clefting.
While studying the structure of IRF6, the group noticed a sequence variation that they thought might play a role in causing isolated clefts. Such variations, called single nucleotide polymorphisms, or SNPs, occur
Contact: Bob Kuska
NIH/National Institute of Dental and Craniofacial Research