Autosomal dominant arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death in young individuals and athletes. It primarily affects the right ventricle; with time, it may also involve the left ventricle. The presentation of disease is highly variable even within families, and affected individuals may not meet established clinical criteria. The mean age at diagnosis is 31 years (+/-13; range: 4-64 years).
The diagnosis of autosomal dominant ARVD/C is made using a combination of noninvasive and invasive tests to detect abnormalities in cardiac structure and rhythm. The eight genes known to be associated with autosomal dominant ARVD/C are: TGFB3 (locus name: ARVD1; protein: transforming growth factor beta-3), RYR2 (locus name ARVD2; protein: ryanodine receptor 2), TMEM43 (locus name ARVD5; protein: transmembrane protein 43), DSP (locus name ARVD8; protein: desmoplakin), PKP2 (locus name ARVD9; protein: plakophilin-2), DSG2 (locus name: ARVD10; protein: desmoglein-2), DSC2 (locus name: ARVD11; protein: desmocollin-2), and JUP (locus name: ARVD12; protein: junction plakoglobin). Four additional genes associated with autosomal dominant ARVD/C have been mapped but not identified (locus names ARVD3, ARVD4, ARVD6, and ARVD7). Additional loci remain undetermined.
Autosomal dominant ARVD/C is inherited in an autosomal dominant manner. A proband with autosomal dominant ARVD/C may have the disorder as a result of a new gene mutation. The proportion of cases caused by de novo mutations is unknown. Each child of an individual with autosomal dominant ARVD/C has a 50% chance of inheriting the mutation. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation has been identified in the family. Such testing may be available through laboratories that offer either testing for the gene of interest or custom testing.