Hypertrophic Cardiomyopathy: An Overview of Genetics and Management

Abstract

Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac muscle disorder with a diverse natural history, characterized by unexplained left ventricular hypertrophy (LVH), with histopathological hallmarks including myocyte enlargement, myocyte disarray and myocardial fibrosis. Although these features can cause significant cardiac symptoms, many young individuals with HCM are asymptomatic or mildly symptomatic. Sudden cardiac death (SCD) may occur as the initial clinical manifestation. Over the past few decades, HCM has been considered a disease of sarcomere, and typically as an autosomal dominant disease with variable expressivity and incomplete penetrance. Important insights into the genetic landscape of HCM have enhanced our understanding of the molecular pathogenesis, empowered gene-based diagnostic testing to identify at-risk individuals, and offered potential targets for the development of therapeutic agents. This article reviews the current knowledge on the clinical genetics and management of HCM.

Keywords: gene mutation; genetics; hypertrophic cardiomyopathy; inherited cardiomyopathy; sarcomere.

Figure 1

Representation of protein interaction map for genes implicated in hypertrophic cardiomyopathy (HCM). The size of each node (red) is proportional to the relative contribution of each gene to all genotype-positive HCM cases. Predicted interactions are indicated by green color, and the intensity represents correlation score (combined score) between two genes from STRING database (https://string-db.org). The blue dashed circles represent groups of protein classified by the location or role of genes. HCM, hypertrophic cardiomyopathy. DCM, dilated cardiomyopathy.