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Evaluation of Type 5 Long QT Syndrome
Study Questions:
What are the genetic features and clinical phenotypes associated with type 5 long QT syndrome (LQT5)?
Methods:
Patients with either type LQT5 (n = 229) or type 2 Jervell and Lange-Nielsen syndrome (JLNS2, n = 19) were enrolled in this study. Their genetic and clinical features and their outcomes were characterized. An arrhythmic event was defined as an appropriate implantable cardioverter-defibrillator discharge, cardiac arrest, or sudden cardiac death.
Results:
Rare KCNE1 variants were identified in 89 probands and 140 family members with presumed LQT5 and in the 19 JLNS2 patients. Among the LQT5 patients, the probands had a longer QTc than the genotype-positive family members (477 vs. 441 ms). A prolonged QTc was present in 20.7% of the genotype-positive family members. An arrhythmic event occurred in 17% of probands compared to 1.4% of family members. The 10.5% prevalence of an arrhythmic event in the JLNS2 patients did not differ significantly from that of the overall LQT5 cohort. The prevalence of the KCNE1 variants in a human genome database of >140,000 people (0.24%) was >200 times greater than the anticipated prevalence of LQT5.
Conclusions:
KCNE1 variants predispose to LQT5 but have low penetrance and a benign clinical phenotype in approximately 90% of individuals who are genotype-positive.
Perspective:
LQT5 accounts for only 1-2% of all long QT syndrome cases and is caused by loss-of-function of a potassium channel coded for by KCNE1. Because of its scarcity, LQT5 has not been well-characterized until now. The present multicenter study provides important information that has useful clinical implications. Genotype-positive individuals who are phenotype-negative should be counseled to avoid QT-prolonging medications but may not require other measures such as a beta-blocker or exercise restriction.
Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Dyslipidemia, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Lipid Metabolism
Keywords: Arrhythmias, Cardiac, Death, Sudden, Cardiac, Defibrillators, Implantable, Diabetes Mellitus, Type 2, Genome, Human, Genotype, Heart Arrest, Jervell-Lange Nielsen Syndrome, Long QT Syndrome, Patient Discharge, Penetrance, Phenotype, Potassium Channels
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