Arrhythmogenic right ventricular dysplasia (ARVD) is a clinical and pathologic entity for which the diagnosis rests on electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall. It is inherited in an autosomal dominant manner with reduced penetrance and is one of the major genetic causes of juvenile sudden death. When the dysplasia is extensive, it may represent the Uhl anomaly ('parchment right ventricle'). The presenting finding is usually recurrent, sustained ventricular tachycardia with left bundle branch block configuration. Basso et al. (2009) provided a detailed review of ARVD, including diagnosis, pathogenesis, treatment options, and genetics.
Genetic Heterogeneity of Familial Arrhythmogenic Right Ventricular Dysplasia
Other forms of ARVD include ARVD3 (602086), mapped to chromosome 14q12-q22; ARVD4 (602087), mapped to chromosome 2q32.1-q32.3; ARVD5 (604400), caused by mutation in the TMEM43 gene (612048) on chromosome 3p23; ARVD6 (604401), mapped to chromosome 10p14-p12; ARVD8 (607450), caused by mutation in the DSP gene (125647) on chromosome 6p24; ARVD9 (609040), caused by mutation in the PKP2 gene (602861) on chromosome 12p11; ARVD10 (610193), caused by mutation in the DSG2 (125671) on chromosome 18q12; ARVD11 (610476), caused by mutation in the DSC2 gene (125645) on chromosome 18q12.1; ARVD12 (611528), caused by mutation in the JUP gene (173325) on chromosome 17q21; ARVD13 (615616), caused by mutation in the CTNNA3 gene (607667) on chromosome 10q21; ARVD14 (618920), caused by mutation in the CDH2 gene (114020) on chromosome 18q12; and ARVD15 (see 617047), caused by mutation in the FLNC gene (102565) on chromosome 7q32.
The designation ARVD2 had been used for patients reported to have a form of arrhythmogenic cardiomyopathy resulting from mutation in the RYR2 gene (180902); it was later recognized that the patients had catecholamine-induced ventricular tachycardia (CPVT1; 604772) rather than arrhythmogenic cardiomyopathy (Karmouch et al., 2018).
ARVD7 is a former designation for a form of myopathy and ARVD mapped to chromosome 10q22, which was later found to be a form of myofibrillar myopathy (MFM1; 601419) caused by mutation in the DES gene (125660) on chromosome 2q35.
Christensen et al. (2010) screened 65 ARVD probands for mutations in 5 desmosomal genes as well as the TGFB3 gene (190230), and identified 19 different mutations in the desmosomal genes in 12 of the families, including 7 with more than 1 mutation. In 6 families, digenic mutation carriers were identified, with at least 1 of the mutations being absent in the control population. The authors stated that their findings partially supported a gene dosage effect, although phenotypic variation was large.
Nitoiu et al. (2014) reviewed desmosome biology in cardiocutaneous syndromes and inherited skin disease, including discussion of the involvement of the DSP, PKP2, DSG2, DSC2, and JUP genes. [from
OMIM]