Genetics and Genomics of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an unexplained left ventricular hypertrophy (LVH) in the absence of precipitating factors such as hypertension or aortic stenosis. HCM is a disease of enormous phenotypic and genotypic heterogeneity. Affecting 1 in 500 people, it is the most prevalent genetic cardiovascular disease. It can manifest itself with negligible to extreme hypertrophy, minimal to extensive fibrosis and myocyte disarray, absent to severe left ventricular outflow tract obstruction, and distinct patterns of hypertrophy. The clinical presentation of HCM is underscored by extreme variability from an asymptomatic course to that of severe heart failure and arrhythmias. It commonly manifests itself between the second and the fourth decades of life, but can present itself at the extremes of age. Infants and young children may be affected with severe hypertrophy leading to heart failure, and these patients have poor prognosis. The most common symptoms are exertional dyspnea, chest pain, and syncope or presyncope. Approximately 5% of patients with HCM progress to "end-stage" disease characterized by left ventricular dilatation and heart failure. In such cases, cardiac transplantation may be considered. Other serious life-threatening complications include embolic stroke and cardiac arrhythmias. Genetic and clinical screening of family members with HCM plays an important role in its early diagnosis. © 2010