Discovery of susceptibility genes for Down syndrome-associated congenital heart defects using whole genome sequencing

Children with Down syndrome (DS), which occurs due to trisomy 21, have a 2000-fold increased risk of atrioventricular septal defects and a 50-fold increased risk of congenital heart defects overall, but why this increased vulnerability exists in unknown. The aim of this study is to identify genetic variants underlying this increased risk in children with DS. Insights into the genes and perturbed pathways that drive this risk for abnormal heart development will have implications for improved genetic counseling, surveillance, clinical management, and treatment strategies for both children with and without DS.