Arrhythmogenic right ventricular dysplasia

Arrhythmogenic right ventricular dysplasia, a cell adhesion cardiomyopathy: insights into disease pathogenesis from preliminary genotype—phenotype assessment

A A Tsatsopoulou1, N I Protonotarios1 and W J McKenna2
1) Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece
2) Department of Medicine, University College London and University College London Hospitals Trust, London, UK

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is a genetically determined heart muscle disorder presenting clinically with even lethal ventricular arrhythmias, particularly in the young and athletes. It is reported familial with recessive and most commonly dominant inheritance. Disease-causing genes are increasingly recognised among desmosomal proteins plakoglobin, desmoplakin, plakophilin2, and desmoglein2 displaying phenotypic heterogeneity. Mutations in the plakoglobin and desmoplakin genes have been identified to underlie recessive ARVC associated with woolly hair and palmoplantar keratoderma (Naxos disease), while mutations in plakophilin2, desmoglein2 as well as desmoplakin have been identified to underlie the dominant non-syndromic form. Preliminary genotype–phenotype assessment indicates that mutations affecting the outer dense plaque of desmosome (desmoglein2, plakoglobin, plakophilin2 and the N-terminal of desmoplakin) result in ARVC with the ordinary described phenotype. However, mutations at the inner dense plaque, particularly affecting the desmin-binding site of desmoplakin, may result in ARVC with predominantly left ventricular involvement and clinical overlapping with dilated cardiomyopathy. The interesting finding of abnormal distribution of plakoglobin, independently of the primarily affected protein, might suggest a common pathway for plakoglobin in ARVC pathogenesis.

Abbreviations: ARVC, arrhythmogenic right ventricular dysplasia/cardiomyopathy; DCM, dilated cardiomyopathy
Keywords: arrhythmogenic right ventricular dysplasia/cardiomyopathy; Naxos disease; cell-adhesions; desmosomal proteins; sudden death

Heart 2006;92:1720-1723

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society