Arrhythmogenic right ventricular cardiomyopathy: a 'final common pathway' that defines clinical phenotype

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a primary heart muscle disease with distinct characteristics. ARVD/C predominantly affects the right ventricle (RV), with RV dilation and thinning due to fibrofatty infiltration of the ventricular myocardium, and ultimately depressed systolic function leading to right heart failure or biventricular failure. 1 Early in its clinical course, ARVD/C typically presents with ventricular arrhythmias (usually with a left bundle branch pattern), syncope, or sudden cardiac death. 2 Tragically, this clinical scenario commonly occurs in young, healthy, athletic individuals. A set of clinical criteria, known as the ‘Task Force Criteria’, first described by McKenna et al. 3 in 1994 and later modified for inclusion of family members, 4 utilizes electrical, myocardial and clinical features to clinically diagnose patients with this disorder. 3, 4 The familial nature of ARVD/C has been recognized for many years but the underlying genetic and mechanistic basis of the disease has only recently come to light. The disease is transmitted with an autosomal dominant trait, although autosomal recessive disease with complex phenotype including associated skin and hair abnormalities is also well described. 5 In the majority of cases, penetrance appears to be low, usually well below 50%. In the early 1990s, we proposed that similar clinical phenotypes occur based on disruption in ‘final common pathways’ by direct mutation in genes encoding proteins in a … *Corresponding author. Tel: +1 832 826 5651; fax: +1 832 825 5921. E-mail address: jtowbinatbcm. tmc. edu