Long QT Syndromes Are Heterogeneous Disease Entities Presenting not only QT Prolongation but Multiple Phenotypes—Cases with Compound Heterozygous Mutations

Long QT syndromes (LQTS) consist of heterogeneous disease entities characterized by a remarkable prolongation of QT interval on ECG and a peculiar polymorphic ventricular tachycardia called “torsade de pointes” , which often degenerates into ventricular fibrillation and causing cardiogenic syncope or sudden death. Because of extensive studies on familial LQTS patients using the molecular genetics since early 1990s, it has been shown that genetic variants in genes encoding cardiac ion channels or their modulating proteins cause the delayed repolarization of ventricular action potential and thereby QT prolongation as a phenotype. Up to date, a variety of mutations in 13 different genes have been shown to be associated with LQTS. In the clinical setting, however, the first three subtypes (LQT1-3) are most frequently seen and presenting quite different phenotypes. Because the gene responsible for each subtype encodes a distinct ion current (IKs, IKr and INa), it is no wonder that the malfunction of specific channel leads to different clinical features. On a thorough screen for candidate genes in our multicenter study, in addition, we recognized that there were a substantial number of compound mutation cases (26 among 310 probands, 8.4%). In this symposium, we would like to make a brief overview on Japanese LQTS.