There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
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.