Abstract 16769: QT Prolongation and Variability Among Patients With Rett Syndrome

Abstract

Introduction: Rett syndrome (RTT) is caused by mutations in the MECP2 genes resulting in various neurological, gastrointestinal, and respiratory symptoms. Prolonged corrected QT interval (QTc) is also reported and thought to be a cause of sudden death in RTT. However, characterization of QTc, its clinical correlation, and association with other clinical features of RTT has been limited. For example, while the incidence of prolonged QTc in RTT varies widely in previous reports, no previous studies have looked at QTc variability, which is an important electrophysiological characteristic affecting both the incidence of prolonged QTc and risk of sudden death. Hypothesis: QTc in RTT has a greater variability than QTc in a healthy age-and-gender matched historical control. Methods: Retrospective chart review of RTT patients with serial electrocardiograms (ECGs) was performed. Each ECG was manually read by two pediatric cardiologists, and the QTc was calculated using Bazett’s formula. ECGs while a patient was given potentially QTc prolonging medications were excluded. Prolonged QTc was defined as ≥ 460 ms for pre-pubertal and ≥ 480 ms for post-pubertal females. QTc variability, defined as the difference of the maximum and minimum QTc, was calculated for each patient and compared to a healthy age-and-gender matched historical control. Results: A total of 30 RTT patients (all females) and 116 ECGs were included in the study. The mean QTc was 442 ms (383—534 ms).Patient age rage was from 1- 45 years. The mean intra-subject variability in QTc in our patient cohort was significantly greater than that of the control cohort (16.5 ms vs. 8.1 ms, P < 0.001). Twenty-one patients (70%) had variability greater than 2 standard deviations of the control group. The mean inter-subject variability in QTc was 26.8 ms (1.4 - 42 ms). The incidence of prolonged QTc in our cohort was 60% (18/30). However, the incidence of persistent prolonged QTc was 7% (2/30). Conclusions: QTc in RTT has a significantly larger variability than that of healthy controls. Given this QTc variability over time and its assocaition with increased risks of sudden death, serial evaluation of not only QTc but also QTc variability and dispersion should be part of the routine cardiac evaluation of RTT patients.