Researchers have developed a new genetic test that can help predict whether parents who have one child with the "isolated" form of cleft lip or palate are likely to have a second child with the same birth defect. Isolated clefts account for 70 percent of all cleft lip and palate cases.
The National Institute of Environmental Health Sciences, the National Institute of Dental and Craniofacial Research, and the National Institute of General Medical Sciences provided funding for the study. All three agencies are components of the National Institutes of Health. The study results appear in the August 19 issue of the New England Journal of Medicine.
"This study shows that we've reached a point where it's possible to take blood samples from parents, test certain genes, and determine whether their risk for a second child with cleft lip or palate is, say, 1 percent or 20 percent," said Jeffrey Murray, M.D., a scientist at the University of Iowa and senior author on the study. "Now is the time to begin thinking about how best to apply these types of tests clinically and ensure that they truly benefit the families and their children."
Isolated clefts arise during fetal development from a dynamic interplay of genes, diet, and environmental factors, and current research tools are just beginning to cut through the complexity. Though the condition is usually correctable with several surgeries, families undergo tremendous emotional and economic hardship during the process. Children with this condition often require many other services, including complex dental care and speech therapy.
"These results show that a specific gene plays a crucial role in the development of isolated cleft lip and palate," said Dr. Kenneth Olden, director of NIEHS. "This discovery will provide parents with important information that will enable them to make informed decisions about future pregnancies."
According to Murray, babies born with the isolated form of cleft lip and palate do not have other birth defects often associated with this condition. Roughly one in every 600 babies in the United States is born with the isolated cleft lip and palate.
The authors say this latest gene test, when used with parents who already have one child with isolated cleft lip and palate, can predict this birth defect in subsequent children about 12 percent of the time. Utilizing this new gene test along with others that have already been developed, scientists now can collectively predict about 15 percent of isolated cleft lip and palate cases, impossible just a few years ago.
One of the first diagnostic tools of its kind, the gene test is based on distinct mutations in and around the gene IRF6, which encodes a specific protein that plays a vital role in the normal formation of the lips, palate, skin and genitalia during the early stages of development. The researchers found that mutations of the IRF6 gene are associated with an increased chance that a child would be born with a cleft lip or palate.
Two years ago, Murray and colleagues found that the IRF6 gene plays a role in Van der Woude Syndrome, a condition in which babies are born with clefts that are accompanied by other birth defects. There are more than 150 such syndromes, accounting for the remaining 30 percent of all cleft lip and palate.