Identical pathogenic sarcomere gene mutations in 3 father-son pairs with hypertrophic cardiomyopathy resulted in vastly different phenotypes and clinical presentations.
Case Report (n=6)
Identical HCM gene mutations can result in vastly different clinical phenotypes even among first-degree relatives, highlighting the limitations of a classical monogenic model.
Hypertrophic cardiomyopathy (HCM) is a genetic disease with variable penetrance and expressivity. Even in first-degree family members with the same pathogenic sarcomere gene mutation, there can be a wide array of clinical presentations, ranging from asymptomatic to sudden cardiac death. In this case series, we report 3 father-son pairs who have identical gene mutations but vastly different phenotypes and clinical presentations. Our findings highlight the importance of gene testing in identifying patients with HCM and subsequent risk stratification. These cases highlight the limitations of a classical monogenic HCM model and suggest that a more inclusive endophenotypic model may be more appropriate.
Bavishi et al. (2026) conducted a case report in Hypertrophic cardiomyopathy (n=6). Pathogenic sarcomere gene mutation was evaluated. Identical pathogenic sarcomere gene mutations in 3 father-son pairs with hypertrophic cardiomyopathy resulted in vastly different phenotypes and clinical presentations.