Thanks to surgery, about 90 percent of infants born with congenital heart disease (CHD) survive to adulthood, but many face a lifetime of related health problems such as neurodevelopmental abnormalities, respiratory problems, and heart arrhythmias.
“We are great at fixing the plumbing but not at fixing the patient,” said Martina Brueckner, professor of pediatrics and genetics at the Yale School of Medicine.
Thanks to a massive analysis of genes from 2,871 CHD patients and their families, Brueckner and the Pediatric Cardiac Genomics Consortium have uncovered links between the birth defect and conditions such as autism and respiratory disorders.
Their research was published Oct. 9 in the journal Nature Genetics.
Congenital heart disease affects about 1% of babies, but its genetic roots are complex and have been difficult to identify. The study used the whole exome approach pioneered by former Yale geneticist and co-senior author Richard Lifton, combined with novel statistical analysis developed by Yale’s Sheng Chih Jin and colleagues at the University of Wisconsin and Harvard University. CHD patients and their families were recruited from nine centers in the United States and University College London, and their genes were sequenced by the Yale Center for Genome Analysis at West Campus.
The researchers found that many genes already implicated in autism were also associated with CHD, and they found new genes that cause CHD in some patients. Also, the research suggested that some respiratory ailments found in CHD patients are linked to defects in cilia — hairlike structures on the surface of cells that carry out a host of biological functions. The findings could help with counseling affected families regarding the risk for recurrence of CHD, the authors say.
“It has been frustrating to see one patient recover nicely and another with the exact same heart defect struggle,” Brueckner said. “This type of study helps us understand why and is a step toward personalized treatment.”
Christine Seidman of Harvard Medical School and Brigham and Women’s Hospital is co-senior author of the paper. Yale’s Jin and Samir Zaidi are co-first authors of the paper along with Harvard’s Jason Homsy.
Primary funding for the study was provided by the National Institutes of Health.