Genes Found Linking Infants' Heart Disease and Brain Development

Sometimes when a young life begins with heart problems, those problems truly are just the beginning. Half of infants born with severe congenital heart disease go on to develop neurodevelopmental disorders, which may include cognitive, motor, social, and language impairments. Doctors have not definitively explained the causes for the developmental delays, but likely explanations include side effects from cardiac surgery early in life, complications during pregnancy co-occurring with the child’s developing heart disease, and genetic risk factors.

A team of researchers from the Pediatric Cardiac Genomics Consortium studying the role of genetics in congenital heart disease has now confirmed their longstanding suspicion: Some of the same gene defects underlie certain cases of congenital heart malformations and neurodevelopmental disorders.

“Congenital heart disease is the most frequent serious birth defect, so as we discover more of these gene alterations, we will be better able to provide genetic counseling and refine patient care for many families and children,” said Elizabeth Goldmuntz, MD, FAAP, FACC, a cardiologist at The Children’s Hospital of Philadelphia, and professor at the Perelman School of Medicine at the University of Pennsylvania, and one of the study’s leaders.

The team reported in Science that they found excess rates of damaging de novo genetic mutations — spontaneous mutations arising during embryonic development predicted to change the function of the encoded protein— in children with moderate to severe congenital heart disease and neurodevelopmental delay and/or other non-cardiac birth defects, compared to children with congenital heart disease alone. Their study included 1,213 children with congenital heart disease and their parents.

Researchers sequenced the whole exome, or expressed part of the genome, from each trio of participants, to identify damaging mutations in the child’s genes that did not come from either parent. These damaging mutations disproportionately occurred in genes for developmental processes that are highly expressed in the developing heart and brain. The findings may allow researchers to tailor future treatments to children based on their personal genetic risk.

It may be possible to identify the cardiac population at higher risk for neurodevelopmental disorders and then intervene earlier on, when the brain is still developing, Dr. Goldmuntz noted to The Philadelphia Inquirer. These earlier interventions may improve the chances of having a lasting impact, she said.

Other study leaders included researchers from other member centers of the Pediatric Cardiac Genomics Consortium, in addition to CHOP: Mount Sinai School of Medicine, Yale University, Harvard University, and Columbia University. The study was funded by the National Heart, Lung and Blood Institute as part of a Bench to Bassenett program, designed to enhance cross-talk between basic science and clinical care.

To learn more about the study, visit the CHOP press release and the NIH press release and Philadelphia Inquirer article.