Mutations in approximately 18 genes cause inherited cardiomyopathies via defective force generation, defective force transmission, myocardial energy deficits, and abnormal calcium homeostasis.
This review highlights the genetic mutations and pathophysiological mechanisms underlying inherited cardiomyopathies, which may guide future diagnostic and therapeutic approaches.
Cardiomyopathies are diseases of heart muscle that may result from a diverse array of conditions that damage the heart and other organs and impair myocardial function, including infection, ischemia, and toxins. However, they may also occur as primary diseases restricted to striated muscle. Over the past decade, the importance of inherited gene defects in the pathogenesis of primary cardiomyopathies has been recognized, with mutations in some 18 genes having been identified as causing hypertrophic cardiomyopathy (HCM) and/or dilated cardiomyopathy (DCM). Defining the role of these genes in cardiac function and the mechanisms by which mutations in these genes lead to hypertrophy, dilation, and contractile failure are major goals of ongoing research. Pathophysiological mechanisms that have been implicated in HCM and DCM include the following: defective force generation, due to mutations in sarcomeric protein genes; defective force transmission, due to mutations in cytoskeletal protein genes; myocardial energy deficits, due to mutations in ATP regulatory protein genes; and abnormal Ca2+ homeostasis, due to altered availability of Ca2+ and altered myofibrillar Ca2+ sensitivity. Improved understanding that will result from these studies should ultimately lead to new approaches for the diagnosis, prognostic stratification, and treatment of patients with heart failure.
Fatkin et al. (2002) conducted a review in Inherited Cardiomyopathies. Mutations in approximately 18 genes cause inherited cardiomyopathies via defective force generation, defective force transmission, myocardial energy deficits, and abnormal calcium homeostasis.