About this condition
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy and the leading cause of sudden cardiac death in young athletes. It affects approximately 1 in 500 people (1 in 250 when genetic screening is applied), though actual prevalence may be higher due to incomplete penetrance. HCM is characterized by unexplained left ventricular hypertrophy, typically with asymmetric septal thickening, in the absence of abnormal loading conditions. The condition follows autosomal dominant inheritance with variable expressivity and age-related penetrance — some variants have >90% penetrance by adulthood, while others remain clinically silent in some carriers.
Two genes, MYH7 and MYBPC3, together account for 70–80% of genetically identified HCM cases. MYH7 variants (encoding beta-myosin heavy chain) are predominantly missense mutations and are associated with higher penetrance, earlier disease onset, and more severe hypertrophy. MYBPC3 variants (encoding cardiac myosin-binding protein C) are predominantly truncating and associated with later onset but still significant disease. At least eight sarcomere genes are now recognized as HCM-causing, each with distinct penetrance and phenotypic implications. Approximately 60% of HCM is familial; the remaining cases result from de novo variants.
Identifying a sarcomere mutation has profound implications for patient care and family counseling. Genetic testing enables cascade screening of family members — asymptomatic relatives may harbor pathogenic variants and warrant initiation of serial cardiac surveillance with echocardiography and ECG. Once identified, carriers benefit from activity restriction (avoiding intense competitive sports), medical therapy with beta-blockers or calcium channel blockers, and periodic assessment. Genetic information also informs family planning, prenatal testing, and preimplantation genetic diagnosis for families with known mutations, offering reproductive options.
MYH7 and MYBPC3 variants differ markedly in their inheritance patterns and phenotypic severity — MYH7 typically earlier-onset and more severe, MYBPC3 later-onset but with significant progression risk.
- Gene locus
- MYH7 (14q11.2), MYBPC3 (11p11.2)
