The phenotype characteristics of type 13 long QT syndrome with mutation in KCNJ5 (Kir3.4-G387R)

Abstract

Background: Long QT syndrome type 13 (LQT13) is caused by loss-of-function mutation in the KCNJ5-encoded cardiac G-protein-coupled inward rectifier potassium channel subtype 4 protein. The electrocardiographic (ECG) features of LQT13 are not described yet.

Objective: To describe for the first time in detail the phenotype-genotype relationship of the ECG and clinical features in patients with LQT13.

Methods: The 12-lead ECGs, 24-hour Holter recordings, and clinical information from KCNJ5-G387R mutation carriers of a fourth-generation Han Chinese family with LQT13 and a group of healthy Chinese individuals were analyzed.

Results: Compared with the analysis of the healthy group (n = 8), age- and sex-matched pair analysis revealed that the mutation carriers (n = 8) had ventricular repolarization abnormality results in the prolongation of corrected QT and QTpeak intervals (P < .01); greater combined measure of repolarization morphology (T-wave morphology combination score) based on asymmetry, flatness, and notch (P < .01); and reduced low frequency/high frequency ratio of heart rate variability (P < .01) as a reflection of cardiac autonomic imbalance. Mean heart rate, time domain parameters of heart rate variability, time interval from T-wave peak to T-wave end, and T-wave amplitude were similar.

Conclusions: This study demonstrates for the first time the ECG features of patients with LQT13. Our data suggest that QTpeak intervals and T-wave morphology combination score may be the better parameters than the corrected QT interval to predict the phenotype-genotype relationship in patients with LQT13.

Keywords: AAI; AF; APD; AVB; ECG; G-protein coupled inward rectifier potassium channel subtype 4 protein; GIRK4; HRV; Heart rate variability; I(K,ACh)(I(GIRK)); Kir3.4 (GIRK4); LF/HF; LQT13; LQTS; MCS; Morphology combination score; QT; QTc; QTcF; RMP; T-wave morphology; T-wave morphology combination score; TpTe; VVI; acetylcholine/adenosine-induced potassium current; action potential duration; atrial fibrillation; atrioventricular block; atrium paced, atrium sensed, and pacemaker inhibited in response to sensed beat; corrected QT interval; corrected QT interval for heart rate using the formula QTcF = QT/RR(1/3); electrocardiogram/electrocardiographic; heart rate variability; long QT syndrome; long QT syndrome type 13; low frequency/high frequency ratio; resting membrane potential; time interval from T-wave peak to T-wave end; ventricle paced, ventricle sensed, and pacemaker inhibited in response to sensed beat.