Clinical and genetic heterogeneity of dilated cardiomyophathy. Review

This article contains an overview of published scientific sources from the MEDLINE database on the PubMed, Web of Science, Scopus platforms regarding the dilated cardiomyopathy with an emphasis on clinical and genetic aspects. Taking into account the etiological origins, various classification categories of myocardial damages are presented — non‑syndromic, acquired (secondary), syndromic cardiomyopathies. The modern definition of dilated cardiomyophaty is presented in accordance with the recommendations of international experts. The review focuses on cardiomyocyte components that are important for energy generation and transmission, mechanical and signaling functions, and maintenance of electrolyte homeostasis. A list of genes encoding contractile proteins and their regulatory elements in components of sarcomeres, Z‑disks, cytoskeletons, desmosomes, and ion channels of cardiomyocytes is provided. The role of pathogenic gene variants associated with mechanisms contributing to the initiation, clinical manifestation, and prognosis of dilated cardiomyopathy is summarized. The causal relationships of mutations in the relevant genes with various clinical scenarios of dilated cardiomyopathy are shown: onset of the diseases, structural myocardial disorders, arrhythmogenic complications, and progression of heart failure. Genetic analysis has become a stimulus for enriching the classification spectrum of cardiomyopathies through the creation of new terms. Specific forms of cardiomyophaties include desmosomal‑dependent cardiomyophathy, desmoplakin cardiomyophathy, RBM20 cardiomyophathy, and others. The argumentation for the further introduction of genetic testing into clinical practice is underlined for the purpose of personalized management of patients with cardiomyopathies and timely identification of risk factors for the disease in their family members at the pre‑nosological stage.