Phenotypic Overlap between Long QT Syndrome Type 1 and Brugada Syndrome: Possible Insights into Monogenic and Polygenic Architecture

Long QT syndrome (LQTS) and Brugada syndrome (BrS) are inherited arrhythmia syndromes associated with sudden cardiac death. LQTS is generally considered as a monogenic channelopathy caused by pathogenic variants in genes such as KCNQ1, KCNH2 and SCN5A encoding cardiac ion channels.(1,2) In contrast, BrS is not always monogenic but recently recognized as a genetically complex disorder in which oligogenic or polygenic susceptibility may substantially contribute to the phenotype.(3) Moreover, phenotypic overlap between LQTS and BrS has been reported; most overlapped cases were LQTS type 3 (LQT3) and BrS caused by some particular SCN5A variants, such as E1784K,(4) producing combined gain- and loss-of-function effects in Nav1.5 channel.(5)