Abstract
Inherited cardiomyopathies form a heterogenous group of disorders that affect the structure and function of the heart. Defects in the genes encoding sarcomeric proteins are associated with various perturbations that induce contractile dysfunction and promote disease development. In this review we aimed to outline the functional consequences of the major inherited cardiomyopathies in terms of myocardial contraction and kinetics, and to highlight the structural and functional alterations in some sarcomeric variants that have been demonstrated to be involved in the pathogenesis of the inherited cardiomyopathies. A particular focus was made on mutation-induced alterations in cardiomyocyte mechanics. Since no disease-specific treatments for familial cardiomyopathies exist, several novel agents have been developed to modulate sarcomere contractility. Understanding the molecular basis of the disease opens new avenues for the development of new therapies. Furthermore, the earlier the awareness of the genetic defect, the better the clinical prognostication would be for patients and the better the prevention of development of the disease.
Highlights
Inherited cardiomyopathies form a heterogeneous group of cardiac disorders characterized by structural and/or functional disturbances in the myocardium.Inherited cardiomyopathies have been described as a known cause of heart failure, arrythmia, and sudden cardiac death [1,2,3]
Over the past two decades, numerous mutations in sarcomeric proteins have been well established as the cause of different types of inherited cardiomyopathies (Figure 2), the molecular mechanisms underlying the transition from the mutation to the cardiac phenotype is not fully understood
Distinct sarcomeric and non-sarcomeric mutations were found to be associated with inherited restrictive cardiomyopathy (RCM) such as troponin T (TNNT2), alpha cardiac actin (ACTC), myosin-binding protein C (MYBPC3), tropomyosin 1 (TPM1), myosin light chain 2 (MYL2)
Summary
Inherited cardiomyopathies form a heterogeneous group of cardiac disorders characterized by structural and/or functional disturbances in the myocardium. Inherited cardiomyopathies have been described as a known cause of heart failure, arrythmia, and sudden cardiac death [1,2,3]. As defined by Elliot et al., 2008, cardiomyopathies are classified according to functional and morphological features into four major types: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), and arrhythmogenic cardiomyopathy (ACM). Over the past two decades, numerous mutations in sarcomeric proteins have been well established as the cause of different types of inherited cardiomyopathies (Figure 2), the molecular mechanisms underlying the transition from the mutation to the cardiac phenotype is not fully understood.
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