Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling.

中文翻译：

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小儿心肌病从头变异研究。

小儿心肌病可能是由编码心肌细胞中肌节和细胞骨架的基因变异引起的。变体通常以常染色体显性方式遗传并具有可变的表达性。从头开始有变种报道，但是总体上未知。我们试图确定诊断为肥厚性，扩张性或限制性心肌病（HCM，DCM或RCM）的儿童的新生，致病性和可能致病性（P / LP）变异的发生率，并比较患有以下疾病的个体之间的疾病结局并且没有从头开始的变体。回顾性记录审查确定了接受基因测试的126名HCM（55％），DCM（37％）或RCM（8％）≤18岁的个体。总体而言，有50（40％）人的基因检测呈阳性，而18％的P / LP变异是从头发生的。RCM组（80％）的从头变异率高于HCM组（9％）或DCM（20％）。有证据表明一个RCM家庭存在种系镶嵌症。与没有心律失常史（p = .049），心脏骤停（p = .024），住院（p = .041）和心脏移植（p = .030）相比，具有从头变异的患者更有可能）。从头变异的可能性以及对家庭风险和筛查的影响应纳入遗传咨询。