Genetics of Sudden Cardiac Death, the Channelopathies: Today's Perspective and the Future

Abstract

Channelopathy constitute significant proportion of SCD worldwide (around 10% or 370000 deaths annually). Besides LQTS, the channelopathies include Brugada syndrome (BrS), short QT syndrome, Early Repolarization Syndrome (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and congenital sick sinus syndrome. It was constituting a mysterious group of disease until the second half of the last century when Anton Jervell and Fred Lange-Nielsen described Jervell Lange-Nielsen syndrome in 1957.It was late until 1995 where genetic characterization commenced. Later on, the massive genetic information obtained in the field with discovery of genetic heterogeneity and allelic heterogeneity were all part of our new understanding and clues to solve the historical conundrum of channelopathies. Here, we review the genetic basis of sudden cardiac death with a focus on the current knowledge on the genetics of the primary electric disorders caused primarily by mutations in genes encoding ion channels. Diving deep into the genetic details of those syndromes enable us to improve our knowdelege and decode the pathophysiology of those malignant arrhythmias. The ultimate ambition is prevention of channelopathy based sudden cardiac death and associated disorders in human.