Abstract 16835: Double Gene Mutations in Long QT Syndrome Can Cause Significantly Increased Cardiac Event During Childhood
Background: Long QT syndrome (LQTS) can cause syncope, ventricular tachycardia/fibrillation, and/or sudden death. Several disease-causing gene mutations of ion channels have been identified. Occasionally, double gene mutations in one or two genes have been detected. However, it remains unclear whether children who are double mutation carriers exhibit a more severe phenotype than children with single mutations.
Methods: From 1998 to 2012, we detected 123 mutations in 110 pediatric patients with LQTS. The median age at diagnosis was 9.0 years. Among the patients, 97 had single mutation (group S; 51 with LQT1, 42 with LQT2, and 4 with LQT3), and the remaining 13 had two mutations (group D; 2 patients, double mutations in LQT1; 3, double LQT2; 4, LQT1 and LQT2; 2, LQT1 and LQT3; 2, LQT2 and LQT3). The phenotype and Kaplan-Meier event-free rate between groups S and D were compared. Onset of syncope, ventricular tachycardia/fibrillation, implantation of cardioverter-defibrillator (ICD), and sudden cardiac death were defined as cardiac events.
Results: The median age at diagnosis in group D (8.1 years) was similar to that (9.4 years) in group S. The median QTc interval on ECG in group D was 540 msec, which was significantly longer than that in group S (490 msec). Freedom from syncope was significantly (p = 0.02) lower in group D (46% at 5 years, and 39% at 10 years of age) than in group S (91% at 5 years, 68% at 10 years, and 43% at 15 years of age). The median age at onset of syncope in group D (5 years) was significantly lower than that in group S (10 years). Freedom from ICD implantation in group D (100% at 10 years, 89% at 15 years, and 44% at 20 years of age) was significantly (p < 0.001) lower than in group S (100% at 10 years, 100% at 15 years, and 97% at 20 years of age). Freedom from death in group D was 77% at 5 years and 77% at 20 years and no death was noted in group S.
Conclusions: Double mutation carriers once detected in children had high incidence of syncope within the first decade, requiring ICD implantation within the second decade. The mortality of these patients was high within 5 years after birth.
- © 2012 by American Heart Association, Inc.