The Mystery of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

nly 24 years have elapsed from the time that the clinical profile of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) was first de- scribed.1 Since then, this entity has been found to have a prevalence of about 1 in 5000 persons2 and is well recognized in the United States, Europe, and Asia. The usual clinical presentation of ARVD/C is that of palpitations, nonsustained ventricular tachycardia, and sustained ventricular arrhyth- mias. Uncommonly, sudden cardiac death may be the first manifestation of the disease. Most patients with this condition experience the onset of these symptoms between the ages of 20 and 40 years, and the disease shows a predisposition to occur in men. A familial incidence was noted in the early description of the disease. Article p 1799 Certain observations about the disease were intriguing but puzzling. Why did there appear to be a striking incidence of athletic individuals affected by this disease?3 Why is there a predilection for the disease to primarily affect certain loca- tions of the right ventricle: the right ventricular outflow tract, the apex, and the subtricuspid area of the right ventricle, the so-called "triangle of dysplasia"?1 Why is there a latent period for the development of the clinical manifestations of ARVD/C, because it is seldom evident in childhood but is expressed in late puberty, adolescence, or early adulthood? Over the past 10 years, genetic studies have begun to unravel the mysteries underlying ARVD/C and to provide answers to these puzzling observations. In 2000, Bowles and Towbin4 predicted that there would be a "final common pathway," the disruption of which leads to clinical disease development. We now know that ARVD/C is a disease of desmosomal dysfunction. Desmosomes are a family of pro- teins that include junctional plakoglobin, plakophilin, desmo- plakin, desmoglein, and desmocollin, the function of which is to bind the myocardial cells to one another.5 Desmosomes