Aetiology and pathogenesis of hypertrophic cardiomyopathy

The term hypertrophic cardiomyopathy is used to describe an autosomal dominant cardiac disorder, characterized by myocyte hypertrophy and disarray, interstitial fibrosis and small vessel disease, with or without macroscopic hypertrophy. More than 100 mutations in ten genes, all encoding sarcomeric proteins, have been identified as responsible for this disease. Mutations in the genes for β‐myosin heavy chain, myosin binding protein‐C, and cardiac troponin T are the most common. Other genes involved are α‐tropomyosin, cardiac troponin‐I, essential and regulatory light chains, α‐cardiac actin, titin, and α‐myosin heavy chain. Some mutations are more frequently associated with a given phenotype, but no particular phenotype is mutation specific; in fact, some mutations exhibit highly variable clinical, electrocardiographic and echocardiographic manifestations. This variability in the phenotypic manifestations is probably due to the influence of environmental factors and/or modifier genes. While the aetiology of hypertrophic cardiomyopathy has been extensively elucidated, its pathogenesis is not completely understood. Mutated proteins are incorporated in the sarcomere and impair myocyte contractility. This probably triggers the compensatory local release of trophic factors, which influence the development of the typical anatomical features of the disease, with a pathway similar to that observed in secondary, pressure overload hypertrophy. Conclusions: The various pathological cardiac changes seen in hypertrophic cardiomyopathy are probably due to a compensatory response to impaired myocyte function resulting from mutations in the genes encoding sarcomeric proteins.