Sudden cardiac death is defined as an unpredictable death within 24 hours. It is estimated to occur with a frequency of more than 50,000 per year in Japan. The inherited arrhythmogenic diseases associated with the transmembranous
ionic channels, anchoring
proteins or intracellular
calcium regulating
proteins are thought to be responsible for
sudden cardiac death in infants, children, and young adults who have structurally normal hearts. Recent genetic analyses have identified congenital diseases such as the
long-QT syndrome (LQTS), the
Jervell and Lange-Nielsen syndrome (JLNS), the
Brugada syndrome (BrS), the
short-QT syndrome (SQTS), the
arrhythmogenic right ventricular cardiomyopathy type 2 (ARVC2), and the
catecholamine-induced polymorphic ventricular tachycardia (CPVT) /
familial polymorphic ventricular tachycardia (FPVT). Loss of function in the slow component of the delayed rectifier
potassium current (I(Ks)) channels (KCNQ1, KCNE1), the rapid component of the
potassium current (I(Kr)) channels (KCNH2, KCNE2) and the inward rectifier
potassium current (I(Kl),
Kir2.1) channel (KCNJ2) is linked to the LQTSs (type 1, 2, 5, 6, and 7 (
Andersen syndrome)) and the JLNSs (type 1 and 2). Changes of function in the alpha-subunit of cardiac
sodium channels (SCN5A) is also linked to the LQTS type 3 and the BrS. A mutation in the
ankyrin-B, anchoring
proteins, has been identified as cause of the LQTS type 4. The SQTS is caused by gain of function in the KCNH2. Further, the missense mutations in the gene encoding
ryanodine receptor 2 (
RyR2) or
calsequestrin 2 (CASQ2) that regulate intra-cardiac
calcium handling is possibly implicated in the ARVC2 and the CPVT/FPVT. Herein, we present a review of the literature regarding the genetic mechanisms of the inherited arrhythmogenic diseases.