The cardiac conduction system can be anatomically, developmentally, and molecularly distinguished from the working myocardium. Abnormalities in cardiac conduction can occur due to a variety of factors, including developmental and
congenital defects, acquired injury or
ischemia of portions of the conduction system, or less commonly due to inherited diseases that alter cardiac conduction system function. So called "idiopathic" conduction system degeneration may have familial clustering, and therefore is consistent with a hereditary basis. This "Molecular Perspectives" will highlight several diverse mechanisms of isolated conduction system disease as well as conduction system degeneration associated with other cardiac and non-
cardiac disorders. The first part of this review focuses on
channelopathies associated with conduction system disease. Human genetic studies have identified mutations in the
sodium channel SCN5A gene causing
tachyarrhythmia disorders, as well as progressive
cardiac conduction system diseases, or overlapping syndromes. Next, the importance of embryonic developmental genes such as homeobox and T-box
transcription factors are highlighted in conduction system development and function. Conduction system diseases associated with multisystem disorders, such as muscular and
myotonic dystrophies, will be described. Last, a new
glycogen storage cardiomyopathy associated with ventricular preexcitation and progressive conduction system degeneration will be reviewed. There are a myriad of mutations identified in genes encoding cardiac
transcription factors,
ion channels, gap junctions, energy metabolism regulators,
lamins and other structural
proteins. Understanding of the molecular and ionic mechanisms underlying cardiac conduction is essential for the appreciation of the pathogenesis of conduction abnormalities in structurally normal and altered hearts.