Genetic cardiomyopathies

Abstract

Purpose of review: To describe recent advancements in cardiovascular genetics made possible by leveraging next-generation sequencing (NGS), and to provide a framework for practical applications of genetic testing for hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular cardiomyopathies (ARVC).

Recent findings: The availability of NGS has made possible extensive reference databases. These, combined with recent initiatives to compile previously siloed commercial and research cardiomyopathy data sets, provide a more powerful and precise approach to cardiovascular genetic medicine. HCM, DCM and ARVC are cardiomyopathies usually inherited in an autosomal dominant pattern. Over 1000 pathogenic mutations have been identified: HCM in genes encoding proteins of the sarcomere, and ARVC in genes encoding proteins of the desosome. DCM shows considerably more diverse ontology, suggesting more complex pathophysiology. In addition to allelic and locus heterogeneity, reduced penetrance and variable expressivity among affected individuals can make the clinical diagnosis of 'familial cardiomyopathy' less apparent.

Summary: Current evidence supports the use of genetic testing in clinical practice to improve risk stratification for clinically affected patients and their at-risk relatives for hypertrophic, arrhythmogenic, and dilated cardiomyopathies. Understanding how to implement genetic testing and to evaluate at-risk family members, provide clinical implications of results as well as discuss limitations of genetic testing is essential to improving personalized care.