Genetics of hypertrophic cardiomyopathy: Cardiologist’s perspective

Hypertrophic cardiomyopathy is the most common monogenic cardiac disorder. Clinical presentation varies widely ranging from asymptomatic to severe left ventricular outflow tract obstruction, and sudden cardiac death. Sarcomeric protein gene mutations are most common contributing to 60%, predominantly involving MYBPC3 and MYH7 genes. Some myocardial storage cardiomyopathies mimic HCM, though does not have myocyte disarray or fibrosis characteristic of HCM and are referred to as HCM phenocopies. Genetic testing is crucial to differentiate HCM phenocopies from HCM as management varies. Among the involved families there is a lot of genetic heterogeneity leading to varying phenotypic expression of disease though carrying the same genetic mutation. For better understanding we describe here the basics of human genetics, define the terminologies used in genetics, and go on to describe the genetic basis of HCM. Genetic mutation leads to altered protein structure which are incorporated in the sarcomere leading to dysregulated contractile function, myocardial disarry and fibrosis leading to various clinical manifestation of HCM . we describe the genetic screening strategies which help in identifying family members carrying the mutation and at risk of disease and help in avoiding unnecessary repeated clinical screening in family members not carrying the mutation. we emphasize Integrating genetic testing into clinical practice for proper management of HCM.