Abstract
Hypertrophic cardiomyopathy (HCM), defined clinically by the presence of unexplained left ventricular hypertrophy, is the most common inherited cardiac disorder. This condition is the major cause of sudden death in the young (<30 years of age) and in athletes. The clinical phenotype is heterogeneous, and mutations in a number of sarcomeric contractile-protein genes are responsible for causing the disease in approximately 60% of individuals with HCM. Other inherited syndromes, as well as metabolic and mitochondrial disorders, can present as clinical phenocopies and can be distinguished by their associated cardiac and noncardiac features and on the basis of their unique molecular genetics. The mode of inheritance, natural history and treatment of phenocopies can differ from those of HCM caused by mutations in sarcomere genes. Detailed clinical evaluation and mutation analysis are, therefore, important in providing an accurate diagnosis in order to enable genetic counseling, prognostic evaluation and appropriate clinical management. This Review summarizes current knowledge on the genetics, disease mechanisms, and correlations between phenotype and genotype in patients with HCM, and discusses the implications of genetic testing in routine clinical practice.
Key Points
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Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder that is defined clinically by the presence of unexplained left ventricular hypertrophy
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HCM is a major cause of sudden cardiac death, especially in the young and in seemingly healthy athletes
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Mutations in genes encoding sarcomeric proteins are detected in 60% of patients with HCM
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Several diseases mimic the phenotypic expression of HCM (phenocopies); it is clinically important to recognize phenocopies as the genetics, clinical management and prognosis of these conditions differ to sarcomeric HCM
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Used appropriately, genetic testing can be important in the prognosis, clinical management and genetic counseling of patients and their families
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Keren, A., Syrris, P. & McKenna, W. Hypertrophic cardiomyopathy: the genetic determinants of clinical disease expression. Nat Rev Cardiol 5, 158–168 (2008). https://doi.org/10.1038/ncpcardio1110
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DOI: https://doi.org/10.1038/ncpcardio1110
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