PubMed 18929331

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv7.1 , Nav1.5

Title: A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation.

Authors: Begoña Benito, Ramon Brugada, Rosa Maria Perich, Eric Lizotte, Juan Cinca, Lluis Mont, Antonio Berruezo, José María Tolosana, Xavier Freixa, Pedro Brugada, Josep Brugada

Journal, date & volume: Heart Rhythm, 2008 Oct , 5, 1434-40

PubMed link:

Type 3 long-QT syndrome (LQT-3) is caused by gain-of-function mutations in the SCN5A encoding the cardiac sodium channel. Familial atrial fibrillation (AF), previously considered a potassium channelopathy, has recently been related to sodium genetic variants, both in isolated forms and in patients with underlying heart disease.The purpose of this study was to describe the first family associating LQT-3 and AF due to a gain-of-function mutation in SCN5A and assess the usefulness of the sodium blocker flecainide in individuals with both phenotypes.Complete family screening was performed after identifying a proband showing paroxysmal AF and a long QT interval suggestive of LQT-3. Secondary causes of AF were ruled out in all individuals. Flecainide was used in two patients for LQT-3 diagnosis and therapeutic treatment of AF. Genetic screening was performed by direct sequencing of the exons and exon-intron boundaries of SCN5A.We identified a three-generation family (eight members), all of them showing long QT intervals. Paroxysmal AF initiated between 20 and 35 years of age in all three adults. The flecainide test led to shortening of the QTc interval. Flecainide was also effective in acutely restoring sinus rhythm. A Y1795C mutation was identified in all members.This is the first report showing an association of familial AF and LQT-3 due to a mutation in SCN5A. This finding provides further evidence of the role of SCN5A in AF. We also confirm the usefulness of flecainide in this particular complex phenotype, both as a diagnostic tool for LQT-3 and as an acute treatment for AF.