The Genetics of Neurodevelopment in Congenital Heart Disease

Congenital heart disease (CHD) is the most common birth anomaly, affecting almost 1% of infants. Neurodevelopmental delay is the most common extracardiac feature in people with CHD. Many factors may contribute to neurodevelopmental risk, including genetic factors, CHD physiology, and the prenatal/postnatal environment. Damaging variants are most highly enriched among individuals with extracardiac anomalies or neurodevelopmental delay in addition to CHD, indicating that genetic factors have an impact beyond cardiac tissues in people with CHD. Potential sources of genetic risk include large deletions or duplications that affect multiple genes, such as 22q11 deletion syndrome, single genes that alter both heart and brain development, such as CHD7, and common variants that affect neurodevelopmental resiliency, such as APOE. Increased use of genome-sequencing technologies in studies of neurodevelopmental outcomes in people with CHD will improve our ability to detect relevant genes and variants. Ultimately, such knowledge can lead to improved and more timely intervention of learning support for affected children.