Hypertrophic cardiomyopathy: from genetics to treatment

AJ Marian - European journal of clinical investigation, 2010 - Wiley Online Library
European journal of clinical investigation, 2010Wiley Online Library
Eur J Clin Invest 2010; 40 (4): 360–369 Abstract Background Hypertrophic cardiomyopathy
(HCM) is the prototypic form of pathological cardiac hypertrophy. HCM is an important cause
of sudden cardiac death in the young and a major cause of morbidity in the elderly. Design
We discuss the clinical implications of recent advances in the molecular genetics of HCM.
Results The current diagnosis of HCM is neither adequately sensitive nor specific. Partial
elucidation of the molecular genetic basis of HCM has raised interest in genetic‐based …
Eur J Clin Invest 2010; 40 (4): 360–369
Abstract
Background  Hypertrophic cardiomyopathy (HCM) is the prototypic form of pathological cardiac hypertrophy. HCM is an important cause of sudden cardiac death in the young and a major cause of morbidity in the elderly.
Design  We discuss the clinical implications of recent advances in the molecular genetics of HCM.
Results  The current diagnosis of HCM is neither adequately sensitive nor specific. Partial elucidation of the molecular genetic basis of HCM has raised interest in genetic‐based diagnosis and management. Over a dozen causal genes have been identified. MYH7 and MYBPC3 mutations account for about 50% of cases. The remaining known causal genes are uncommon and some are rare. Advances in DNA sequencing techniques have made genetic screening practical. The difficulty, particularly in the sporadic cases and in small families, is to discern the causal from the non‐causal variants. Overall, the causal mutations alone have limited implications in risk stratification and prognostication, as the clinical phenotype arises from complex and often non‐linear interactions between various determinants.
Conclusions  The clinical phenotype of ‘HCM’ results from mutations in sarcomeric proteins and subsequent activation of multiple cellular constituents including signal transducers. We advocate that HCM, despite its current recognition and management as a single disease entity, involves multiple partially independent mechanisms, despite similarity in the ensuing phenotype. To treat HCM effectively, it is necessary to delineate the underlying fundamental mechanisms that govern the pathogenesis of the phenotype and apply these principles to the treatment of each subset of clinically recognized HCM.
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