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Sudden cardiac death (SCD), defined as death from a cardiac cause occurring shortly after the onset of symptoms, is most often due to an organic cardiac abnormality such as coronary artery disease or structural heart disease.1 However, death in young, active and previously healthy individuals with no identifiable cause on postmortem examination, termed sudden unexplained death (SUD), constitutes about 5% of SCD. When sudden death of unknown aetiology occurs in a child below 1 year of age, it is termed sudden infant death syndrome (SIDS). Unravelling the mystery surrounding SUD and SIDS has been the focus of research efforts recently.2 ,3 As a result of this increased interest as well as the concurrent advances in molecular, genetic, experimental and clinical sciences, there has been an exponential increase in knowledge about the genetic background of SUD and SIDS in the past two decades. Ion channels of the heart have been found to play an integral role in this ever expanding realm of young unexpected death. Currently, primary arrhythmogenic diseases due to mutant dysfunctional ion channels, referred to as cardiac channelopathies, account for ∼35% of SUD and ∼20% of SIDS cases.4 ,5
The sodium (Na+) channel, a ubiquitous member of the cardiac, neural and muscular conduction systems, has been implicated in the pathogenesis of an array of human disorders. Mutations associated with the cardiac Na+ channel are responsible for a wide spectrum of diseases of which Brugada syndrome (BrS) and congenital long QT syndrome type 3 (LQT3) are the best described.6 The clinical manifestations of cardiac Na+ channel diseases are closely linked to the morphological and functional characteristics of the channel itself.
Spectrum of cardiac Na+ channelopathic diseases
Cardiac conduction disease
Sick sinus syndrome