Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations.
Cardiac sodium channel dysfunction caused by mutations in the SCN5A gene is associated with a number of relatively uncommon arrhythmia syndromes, including long-QT syndrome type 3 (LQT3), Brugada syndrome, conduction disease, sinus node dysfunction, and atrial standstill, which potentially lead to fatal arrhythmias in relatively young individuals. Although these various arrhythmia syndromes were originally considered separate entities, recent evidence indicates more overlap in clinical presentation and biophysical defects of associated mutant channels than previously appreciated. Various SCN5A mutations are now known to present with mixed phenotypes, a presentation that has become known as "overlap syndrome of cardiac sodium channelopathy." In many cases, multiple biophysical defects of single SCN5A mutations are suspected to underlie the overlapping clinical manifestations. Here, we provide an overview of current knowledge on SCN5A mutations associated with sodium channel overlap syndromes and discuss a possible role for modifiers in determining disease expressivity in the individual patient.
Remme
Carol Ann
CA
Department of Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.a.remme@amc.uva.nl
Wilde
Arthur A M
AA
Bezzina
Connie R
CR
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D053840:Brugada Syndrome / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D012804:Sick Sinus Syndrome / Q000235:genetics* / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology
D015222:Sodium Channels