A Multidimensional Approach to Understanding Genetic Diversity, Risk Stratification, and Personalized Interventions in Pediatric Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) in children presents unique challenges distinct from adult manifestations, with potentially devastating consequences, including sudden cardiac death. This comprehensive review synthesizes current evidence on the pathophysiology, clinical presentation, and management of pediatric HCM, highlighting critical differences from adult populations. While affecting approximately 1 in 500 individuals, pediatric HCM demonstrates more significant etiological heterogeneity, with up to 35% of cases stemming from non-sarcomeric causes, including RASopathies, metabolic disorders, and syndromic conditions. This etiological diversity contributes to variable disease trajectories and treatment responses, creating a significant research gap in pediatric-specific management protocols. Current pharmacological approaches primarily employ beta-blockers as first-line therapy, with calcium channel blockers serving as alternatives for intolerant patients. However, these conventional medications manage symptoms without addressing underlying pathophysiology or preventing disease progression. Emerging investigational therapies, including angiotensin receptor blockers and myosin inhibitors like mavacamten, show promise in preliminary studies but lack robust pediatric-specific evidence. Surgical interventions, including septal myectomy and the modified Konno procedure, demonstrate efficacy in medication-refractory cases but carry higher complication risks in younger patients. The critical research gap lies in developing targeted therapeutic approaches for pediatric-specific HCM subtypes, particularly those associated with syndromic and metabolic disorders. Additionally, risk stratification models for sudden cardiac death prevention remain inadequately validated in pediatric populations. This review identifies the urgent need for pediatric-focused clinical trials investigating both conventional and novel therapies alongside the development of age-appropriate risk assessment tools to guide personalized management strategies for this vulnerable population.