The Genetic Workup for Congenital Structural Heart Disease: From Clinical to Genetic Evaluation

Abstract

Genetic testing is an important consideration in all congenital heart conditions. Given that congenital heart diseases (CHDs) are disorders of abnormal heart development, it is probable that pathogenic variants in genes that affect early embryonic differentiation and cardiac organogenesis play a large role in CHD. Over the last 50 years, evidence for genetic contributions to the etiologies of CHD has been reinforced by the discovery of CHD associations with specific chromosomal abnormalities, genomic disorders, and rare single-gene disorders. In these patients, genetic evaluation has clinical utility. Precision genetic diagnosis can guide cardiovascular monitoring protocols, allow for evaluation of developmental anomalies of other organ systems, promote early interventions such as speech and developmental therapies, and direct medical and surgical interventions. Additionally, genetic diagnosis allows cascade testing of at-risk relatives, recurrence risk information determination, and preimplantation and prenatal diagnosis if patient-specific mutations are known. Next-generation sequencing has radically changed genetic testing and has already begun to accelerate the pace of discovery of new single-gene mutations in CHD. This chapter will review an algorithm for the evaluation of CHD, the genetic testing options available to clinicians, appropriate genetic counseling of patients when giving results to the patient, and nongenetic causes of CHD to consider.