SCN5A Mutations in Brugada Syndrome

Study Questions:

What is the prognostic significance of the SCN5A mutation in patients with Brugada syndrome (BS)?


Among 415 patients (mean age 46 years) with BS enrolled in a registry, 60 patients (13.3%) had an SCN5A mutation and the other 355 patients were genotype-negative. Clinical and electrocardiographic characteristics were compared between the two groups, as were cardiac events (first appropriate implantable cardioverter-defibrillator shock, aborted cardiac arrest [ACA], sudden cardiac death) during a mean follow-up of 72 months.


Genotype-positive patients had a first episode of syncope at a younger age (mean age 34 vs. 42 years). There was not a significant difference between the two groups in the prevalence of a type I Brugada pattern or in the inducibility of ventricular tachycardia/fibrillation. The cardiac event rate was 2.5%/year overall and was significantly higher in the genotype-positive patients than in the genotype-negative patients. Among 228 patients who were asymptomatic at the time of enrollment, the cardiac event rate during follow-up was 0.9%/year, with no significant difference between the genotype-positive and genotype-negative patients. By multivariate analysis, genotype-positivity and a history of ACA were the only significant predictors of cardiac events.


BS patients who have an SCN5A mutation experience syncope at a younger age and have a higher risk of cardiac events during follow-up.


In the BS, SCN5A mutations cause a reduction in the inward sodium current and are associated with an acceleration in myocyte apoptosis. This results in conduction abnormalities and fibrosis that increase the risk of a malignant ventricular arrhythmia, perhaps explaining why genotype-positivity was associated with a higher rate of cardiac events in this study.

Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents

Keywords: Apoptosis, Arrhythmias, Cardiac, Brugada Syndrome, Death, Sudden, Cardiac, Defibrillators, Implantable, Genetic Association Studies, Genotype, Heart Conduction System, Mutation, Syncope, Tachycardia, Ventricular, Ventricular Fibrillation

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