Puberty-Associated Emergence of Hypertrophic Cardiomyopathy: When Genetics Meets Growth

Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disease with variable and incomplete penetrance, with phenotypic expression occurring across developmental stages, potentially influenced by hormonal and other biological modifiers. Genotype-positive individuals may remain phenotype-negative during childhood, with phenotypic expression emerging during adolescence or early adulthood. Factors influencing the timing of phenotypic conversion remain incompletely understood.

A 13-year-old asymptomatic boy with a strong family history of hypertrophic obstructive cardiomyopathy underwent routine cardiology follow-up. Previous cardiac evaluation at age 9 demonstrated normal electrocardiographic and echocardiographic results. At age 13, coinciding with pubertal development, new-onset asymmetric septal hypertrophy with systolic anterior motion and left ventricular outflow tract obstruction was identified on echocardiography. Cardiac magnetic resonance confirmed significant septal hypertrophy. Subsequent genetic testing confirmed that the patient had a pathogenic MYH7 variant.

This case illustrates the dynamic penetrance of MYH7-related HCM and highlights adolescence as a potential window for phenotypic emergence, possibly influenced by pubertal hormonal changes. Pubertal growth and associated physiological changes may further modulate disease expression in genetically predisposed individuals. These findings underscore the importance of continued longitudinal surveillance throughout childhood, particularly during periods of rapid somatic growth.

Phenotypic expression of HCM in MYH7 mutation carriers may emerge during periods of somatic growth and hormonal developmental transition. Periods of rapid somatic growth, such as puberty, may represent a critical window for phenotypic evolution, highlighting the importance of repeated and more frequent cardiac screening especially around growth spurts in genotype-positive individuals. Risk stratification and recommendations regarding sports participation in pediatric HCM should be individualized and based on clinical findings, genetic status, and shared decision-making rather than universal restriction.