Arrhythmogenic Right Ventricular Dysplasia, Familial, 12

A number sign (#) is used with this entry because of evidence that arrhythmogenic right ventricular dysplasia-12 (ARVD12) is caused by heterozygous mutation in the gene encoding junction plakoglobin (JUP; 173325) on chromosome 17q21.

For a general phenotypic description and a discussion of genetic heterogeneity of this disorder, see ARVD1 (107970).

Clinical Features

Asimaki et al. (2007) described a German family in which the father and 3 sons had arrhythmogenic right ventricular cardiomyopathy. The proband experienced syncope at age 39 years. After a documented episode of sustained ventricular tachycardia he was admitted to the hospital for further diagnostic evaluation and management. Electrocardiography demonstrated QRS prolongation, T wave inversion, and late potentials in right precordial leads. Angiography showed moderate global right ventricular dilatation and regional wall-motion abnormalities without left ventricular involvement. Sustained monomorphic ventricular tachycardia of left bundle branch block morphology was induced at electrophysiologic study. Biopsy of an endomyocardial sample showed extensive fibrofatty replacement of right ventricular muscle and patchy mononuclear inflammatory infiltrate. These phenotypes led to the diagnosis of arrhythmogenic right ventricular cardiomyopathy. Skin and hair appeared grossly normal. The proband's brothers received diagnoses of arrhythmogenic right ventricular cardiomyopathy after cardiac evaluation on the basis of 12-lead and 24-hour electrocardiography and echocardiographic abnormalities. The father had died at age 70 of heart failure and was presumed to have had the disorder.

Molecular Genetics

In a German family with arrhythmogenic right ventricular cardiomyopathy in a father and 3 sons, Asimaki et al. (2007) identified a novel mutation in the plakoglobin gene, predicted to result in the insertion of an extra serine residue after ser39 in the N terminus of the protein (173325.0002). There were no dermatologic manifestations such as those seen in Naxos disease (601214), a recessive disorder also due to mutation in the plakoglobin gene associated with abnormalities of hair and skin.