SCN5A Mutations in Children

Study Questions:

What are the phenotypic characteristics and risk factors for cardiac events among neonates and children with an SCN5A mutation?


This retrospective, multicenter cohort study included 442 patients ≤16 years of age (median age 8 years) with any type of SCN5A mutation who were followed for a median of 5.9 years. A major cardiac event (MCE) was defined as sudden cardiac death, cardiac arrest, syncope, ventricular tachycardia, or high-degree atrioventricular block.


Sixty-eight percent of patients were asymptomatic at the time of diagnosis. The most common electrocardiographic phenotypes were progressive cardiac conduction disorder (26%), type 3 long QT syndrome (LQT3, 11%), Brugada syndrome (2%), and an overlapping phenotype in 16%. The electrocardiographic phenotype was negative at baseline in 44% of patients. A MCE occurred in 31% of patients during follow-up. The independent risk factors for a MCE were age ≤1 year at diagnosis in a proband (hazard ratio [HR], 35.4) or in a nonproband (HR, 3.2), the presence of a compound mutation (HR, 3.7), and a mutation with both gain- and loss-of-function (HR, 0.5). Ninety-nine percent of asymptomatic children with a negative electrocardiographic phenotype remained asymptomatic during follow-up.


SCN5A mutations in children most commonly are clinically manifest as a cardiac conduction disorder. The independent risk factors for a cardiac event include age ≤1 year at the time of diagnosis, a compound mutation, and a mutation with both gain- and loss-of-function.


In this study, symptomatic children and those with LQT3 had the worst prognosis. Along with the other risk factors found in this study, these results should prove helpful for identifying children with an SCN5A mutation in whom implantation of an implantable cardioverter-defibrillator is appropriate.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, 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 Quality Improvement

Keywords: Arrhythmias, Cardiac, Atrioventricular Block, Brugada Syndrome, Death, Sudden, Cardiac, Defibrillators, Implantable, Electrocardiography, Genetic Association Studies, Long QT Syndrome, Mutation, Risk Factors, Syncope, Tachycardia, Ventricular

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