Age-Dependent Clinical And Genetic Characteristics In Japanese Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (Vol 77, Pg 1534, 2013)

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease caused by desmosomal gene mutations, and presents as ventricular tachycardia and sudden cardiac death. Although the mean age at onset or diagnosis of ARVC/D are reported to be around the 30-40 s, the age-dependent clinical and genetic differences remain unknown. Methods and Results: A total of 35 consecutive Japanese probands (23 male) who were clinically diagnosed with ARVC/D were enrolled in the present study, and genetic analysis of PKP2, DSP, DSG2, and DSC2 was done. The mean age at the first symptom and at diagnosis was 38.6 +/- 14.8 years and 40.5 +/- 17.7 years, respectively. Probands in whom the onset was cardiopulmonary arrest were significantly younger (22.3 +/- 15.3 years) than those with arrhythmia (41.1 +/- 13.2 years) or congestive heart failure (45.7 +/- 8.5 years). On genetic screening, 19 mutation carriers were identified. Although there was no age dependence for each gene mutation carrier, carriers with PKP2 premature stop codon developed the disease at a significantly younger age than other mutation carriers. Conclusions: The initial clinical manifestations in some young probands were very severe, and PKP2 mutations with a premature stop codon would be associated with disease onset at a younger age.