Genetics of congenital heart disease: a narrative review of recent advances and clinical implications

Jun Yasuhara, Vidu Garg, Jun Yasuhara, Vidu Garg

Abstract

Congenital heart disease (CHD) is the most common human birth defect and remains a leading cause of mortality in childhood. Although advances in clinical management have improved the survival of children with CHD, adult survivors commonly experience cardiac and non-cardiac comorbidities, which affect quality of life and prognosis. Therefore, the elucidation of genetic etiologies of CHD not only has important clinical implications for genetic counseling of patients and families but may also impact clinical outcomes by identifying at-risk patients. Recent advancements in genetic technologies, including massively parallel sequencing, have allowed for the discovery of new genetic etiologies for CHD. Although variant prioritization and interpretation of pathogenicity remain challenges in the field of CHD genomics, advances in single-cell genomics and functional genomics using cellular and animal models of CHD have the potential to provide novel insights into the underlying mechanisms of CHD and its associated morbidities. In this review, we provide an updated summary of the established genetic contributors to CHD and discuss recent advances in our understanding of the genetic architecture of CHD along with current challenges with the interpretation of genetic variation. Furthermore, we highlight the clinical implications of genetic findings to predict and potentially improve clinical outcomes in patients with CHD.

Keywords: Congenital heart disease (CHD); clinical outcomes; genetic testing; genetics.

Conflict of interest statement

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tp-21-297). VG serves as an unpaid editorial board member of Translational Pediatrics from Aug 2021 to Jul 2023. The other author has no conflicts of interest to declare.

2021 Translational Pediatrics. All rights reserved.

Figures

Figure 1
Figure 1
Established genetic causes of congenital heart disease. Chromosomal abnormalities, copy number variation and single gene variants are associated with ~40% of congenital heart disease cases but the majority (60%) of congenital heart disease remains unknown. All percentages are approximate based on recent publications (13,21-27). NR, not reported.

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