Genetics of Sudden Cardiac Death

Introduction: Cardiomyopathies (DCM, HCM and ACM) and primary arrhythmogenic disorders (BrS, LQTS and CPVT) are the most common causes of sudden cardiac death (SCD) in young people. Systematic investigations of genome wide SNP, GWAS have enabled the identification of many genetic variants associated with cardiovascular diseases. Body: Genetic testing for cardiomyopathies and inherited channelopathies primarily includes panel testing for genes with definitive and strong evidence, and genes with moderate evidence can be considered. Cardiomyocyte exhibiting proteins, involved in the pathogenesis of the genetic cardiomyopathies, include sarcomeric, cytoskeletal, desmosomal and nuclear envelope proteins. Inherited cardiac channelopathies are caused by mutations in genes encoding cellular structures that affect calcium ion availability or membrane ion channels (sodium, potassium or calcium channels). Common variants associated with SCD included those in genes encoding cardiac ion channels (e.g., SCN5A, KCNQ1, KCNH2), calmodulin (CALM2), sarcomeric proteins (MYH7, MYBPC3, TNN, TNNI3), and desmosomal proteins (RyR2, DES).Conclusions: This review provides evidence that specific genetic variants are associated with an increased risk of SCD. The data emphasizes the importance of genetic screening and early intervention in individuals with a family history of SCD or risk factors for inherited cardiac conditions causing SCD. Gene-specific management of familial cardiomyopathies and inherited cardiac channelopathies causing SCD should be emphasized for further research with the improvement of targeted genetic disorders treatment.