Genetic testing in congenital heart disease: A clinical approach

Abstract

Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.

Keywords: Congenital heart disease; Genetics; Genetic screening; Genetic testing

Core tip: Monogenic models and chromosomal abnormalities have been associated with syndromic and non-syndromic forms of congenital heart disease (CHD), paving the way for genetic investigation and testing to shoulder an important role in patient management. Herein, we present an overview of the role of genetics in CHD, propose various clinical scenarios in which genetic testing may be appropriate, and discuss practical implications with regards to when and how to order genetic tests. Summary tables are provided regarding the various genes implicated in syndromic and non-syndromic forms of CHD and recurrence risks in siblings and offspring.