The genetics of isolated congenital heart disease

The genetic mechanisms underlying congenital heart disease (CHD) are complex and remain incompletely understood. The majority of patients with CHD have an isolated heart defect without other organ system involvement, but the genetic basis of isolated CHD has been even more difficult to elucidate compared to syndromic CHD. Our understanding of the genetics of isolated CHD is advancing in large part due to advances in next generation sequencing, and the list of genes associated with CHD is rapidly expanding. Variants in hundreds of genes have been identified that may cause or contribute to CHD, but a genetic cause can still only be identified in about 20–30% of patients. Identifying a genetic cause for CHD can have an impact on clinical outcomes and prognosis and thus it is important for clinicians to understand when and what to test in patients with isolated CHD. This chapter reviews some of the known genetic mechanisms that contribute to isolated inherited and sporadic CHD as well as recommendations for evaluation and genetic testing in patients with isolated CHD.