James Cynthia A, Syrris Petros, van Tintelen J Peter, Calkins Hugh
Division of Cardiology, Department of Medicine, Johns Hopkins University, Carnegie 568D, 600 N. Wolfe St., Baltimore, MD 21287-0409, USA.
Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, UK.
Eur Heart J. 2020 Apr 7;41(14):1393-1400. doi: 10.1093/eurheartj/ehaa141.
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.
致心律失常性心肌病（ACM）是一种遗传性心肌病，其特征为频发室性心律失常和进行性心室功能障碍。ACM患者心脏性猝死风险升高，且可能是首发症状，尤其在年轻个体和运动员中。本综述描述了目前对ACM遗传结构和ACM发病分子机制的认识。我们考虑一种新出现的ACM遗传阈值模型，即包括已知ACM基因中的致病变异、遗传修饰因子和环境暴露（尤其是运动）在内的多种因素需达到疾病表达阈值。我们还综述了在照料ACM家族中整合遗传学（包括近期发现）的最佳实践，并强调了基因型在管理受影响个体和对家族成员进行预测性检测方面的作用。
