Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu 520-2192, Japan.
Circ J. 2013;77(6):1534-42. doi: 10.1253/circj.cj-12-1446. Epub 2013 Mar 20.
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 30-40s, the age-dependent clinical and genetic differences remain unknown.
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.
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.
致心律失常性右室心肌病/发育不良（ARVC/D）是一种由桥粒蛋白基因突变引起的心肌疾病，表现为室性心动过速和心源性猝死。虽然 ARVC/D 的发病或诊断平均年龄报告在 30-40 多岁，但年龄相关的临床和遗传差异仍不清楚。
本研究共纳入 35 例连续的日本先证者（23 名男性），临床诊断为 ARVC/D，并对 PKP2、DSP、DSG2 和 DSC2 进行基因分析。首发症状和诊断时的平均年龄分别为 38.6±14.8 岁和 40.5±17.7 岁。首发为心搏骤停的先证者明显比首发为心律失常（41.1±13.2 岁）或充血性心力衰竭（45.7±8.5 岁）的先证者年轻。在基因筛查中，发现 19 个突变携带者。尽管每个基因突变携带者没有年龄依赖性，但 PKP2 提前终止密码子的携带者发病年龄明显小于其他突变携带者。
一些年轻先证者的初始临床表现非常严重，并且具有提前终止密码子的 PKP2 突变与更年轻的发病年龄相关。
