Genetic Basis for Cardiac Arrhythmias

Abstract

Several arrhythmia syndromes that for long were considered idiopathic are now known to have a genetic basis and are caused by mutations in genes primarily encoding ion channels. Mutations in cardiac ion channels lead to abnormal ionic current characteristics via mechanisms, such as defective channel gating or reduction in sarcolemmal channel expression. This results in the electrocardiogram (ECG) features or arrhythmogenesis in the inherited arrhythmia syndromes. The genetic basis for most arrhythmia syndromes is heterogeneous (a given disorder may be caused by mutations in different genes) and evidence for further genetic heterogeneity exists. It is becoming increasingly clear that therapy should take the type of gene affected into consideration (gene-specific therapy). Considerable heterogeneity may exist in disease manifestation (both in severity as well as differences in disease features) among family members carrying the same mutation.