Arrhythmogenic cardiomyopathy (ACM) is a heritable cardiomyopathy characterized by frequent ventricular arrhythmias and progressive ventricular dysfunction. Risk of sudden cardiac death is elevated in ACM patients and can be the presenting symptom particularly in younger individuals and athletes. This review describes current understanding of the genetic architecture of ACM and molecular mechanisms of ACM pathogenesis. We consider an emerging threshold model for ACM inheritance in which multiple factors including pathogenic variants in known ACM genes, genetic modifiers, and environmental exposures, particularly exercise, are required to reach a threshold for disease expression. We also review best practices for integrating genetics-including recent discoveries-in caring for ACM families and emphasize the utility of genotype for both management of affected individuals and predictive testing in family members.

中文翻译：

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遗传学在心血管疾病中的作用：心律失常性心肌病

致心律失常性心肌病 (ACM) 是一种遗传性心肌病，其特征是频繁的室性心律失常和进行性心室功能障碍。ACM 患者心脏性猝死的风险升高，并且可能是出现的症状，尤其是在年轻个体和运动员中。这篇综述描述了目前对 ACM 遗传结构和 ACM 发病机制的分子机制的理解。我们考虑了一种新兴的 ACM 遗传阈值模型，其中需要多种因素，包括已知 ACM 基因中的致病变异、遗传修饰物和环境暴露，特别是运动，才能达到疾病表达的阈值。