Decoding Hearts: Genetic Insights and Clinical Strategies in Congenital Heart Disease

Structural congenital heart disease (CHD) represents a heterogeneous group of cardiac anomalies of variable embryologic and molecular origins. A basic understanding of the genetics implicated in nonsyndromic (isolated) and syndromic structural CHD can better inform management decisions and family counseling. When a fetus or neonate develops CHD as a result of a genetic cause, it can be due to a mutation or a monogenic, oligogenic, or polygenic pathogenic variant. In this review, we summarize basic cardiac embryology in the context of genetic signaling pathways and proteins that are commonly implicated in syndromic and nonsyndromic structural CHD. We also provide an overview of the basic genetic evaluation in infants with common syndromic structural CHD.