Genotype-Phenotype Correlation in the Long-QT Syndrome

• DOI: 10.1161/01.cir.103.1.89
• Publication Date: 2012-06-12T00:09:32Z
• Authors: Peter J. Schwartz; Silvia G. Priori; Carla Spazzolini; Arthur J. Moss; G. Michael Vincent; Carlo Napolitano; Isabelle Denjoy; Pascale Guicheney; Günter Breithardt; Mark T. Keating; Jeffrey A. Towbin; Alan H. Beggs; Paul Brink; Arthur A. M. Wilde; Lauri Toivonen; Wojciech Zareba; Jennifer L. Robinson; Katherine W. Timothy; Valerie Corfield; Duangrurdee Watta...; Clive Corbett; Wilhelm Haverkamp; Eric Schulze-Bahr; Michael H. Lehmann; Ketty Schwartz; Philippe Coumel; Raffaella Bloise
• Keywords: Sudden Death

Background —The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding the electrophysiological consequences these opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that conditions (“triggers”) associated with events may in large part be gene specific. Methods and Results —We identified 670 LQTS patients known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, arrest, sudden death) examined whether 3 specific triggers (exercise, emotion, sleep/rest without arousal) differed according to genotype. LQT1 experienced majority their (62%) during exercise, only 3% occurred rest/sleep. These percentages were almost reversed among LQT2 LQT3 patients, less likely have exercise (13%) more rest/sleep (29% 39%). Lethal nonlethal followed same pattern. Corrected QT interval did not differ LQT1, (498, 497, 506 ms, respectively). percent free recurrence β-blocker therapy was higher death rate lower (81% 4%, respectively) than (59% (50% 17%, patients. Conclusions —Life-threatening arrhythmias tend occur under circumstances a gene-specific manner. data allow new insights into mechanisms relate genes clinical manifestations offer possibility complementing traditional approaches.