Genetics of dilated cardiomyopathy conduction disease☆

Abstract 

In approximately 30 to 50% of cases, dilated cardiomyopathy is the result of mutations in various genes of the cytoskeletal, sarcomeric, ion channel, signaling and desmosomal pathways. The disease can be complicated by additional problems including cardiac conduction disease and arrhythmia. This is the case of nucleoskeletal genes, in particular the lamin A/C gene, usually associated with autosomal dominant inheritance, and the emerin gene associated with X-linked inheritance. Nucleoskeletal gene mutations can result in supraventricular arrhythmias, atrioventricular block, ventricular arrhythmias and sudden death, frequently requiring a pacemaker or an implantable defibrillator. Up to 30% of patients with atrioventricular block and dilated cardiomyopathy have lamin A/C gene mutations. Cytoskeletal and sarcolemmal genes, such as desmin and dystrophin, have also been associated with specific conduction defects. Desmin cardiomyopathy is characterized by atrioventricular block, whereas X-linked dilated cardiomyopathy due to dystrophin gene mutations frequently shows intraventricular conduction defects, especially right bundle branch block, associated with deep Q waves in the inferior or lateral leads. In the group of ion channels, SCN5A gene mutations cause an autosomal dominant cardiac conduction disorder, progressive atrioventricular and intraventricular conduction delay, sinus node dysfunction, supraventricular arrhythmia, and right and bi-ventricular dilatation and dysfunction. Desmosomal gene mutations (desmoplakin) have been associated with arrhythmogenic left ventricular cardiomyopathy, which, like arrhythmogenic right ventricular dysplasia, are also characterized by ventricular arrhythmias. Finally, storage diseases can cause phenocopies of dilated cardiomyopathy with arrhythmia and conduction defects. Danon disease is typically characterized by Wolff–Parkinson–White pre-excitation, and this can be the first sign of disease particularly in young female carriers. The identification of conduction defects and arrhythmias in the setting of a dilated cardiomyopathy is important clinical clue for the identification of the gene defect.

Keywords: Dilated cardiomyopathy, Conduction disease, Genetics, Muscular dystrophy, Arrhythmia, Sudden death