Agnes Ginges Centre for Molecular Cardiology Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Heath, The University of Sydney, Sydney, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
Agnes Ginges Centre for Molecular Cardiology Centenary Institute, The University of Sydney, Sydney, Australia.
Int J Cardiol. 2021 Feb 1;324:96-101. doi: 10.1016/j.ijcard.2020.09.031. Epub 2020 Sep 12.
Genetic heart disease is a common cause of sudden cardiac arrest (SCA) in the young and those without an ischaemic precipitant. Identifying a cause of SCA in these patients allows for targeted care and family screening. Current guidelines recommend limited, phenotype-guided genetic testing in SCA survivors where a specific genetic condition is suspected and genetic testing is not recommended in clinically-idiopathic SCA survivors.
To investigate the diagnostic utility of broad, multi-phenotype genetic testing in clinically-idiopathic SCA survivors.
Clinically-idiopathic SCA survivors underwent analysis of genes known to be associated with either cardiomyopathy or primary arrhythmia syndromes, following referral to a specialised genetic heart disease clinic in Sydney, Australia between 1997 and 2019. Comprehensive review of clinical records, investigations and re-appraisal of genetic data according to current variant classification criteria was performed.
In total, 22% (n = 8/36) of clinically-idiopathic SCA survivors (mean age 36.9 ± 16.9 years, 61% male) had a disease-causing variant identified on broad genetic testing. Of these, 7 (88%) variants resided in cardiomyopathy-associated genes (ACTN2, DES, DSP, MYBPC3, MYH7, PKP2) despite structurally normal hearts or sub-diagnostic structural changes at the time of arrest, so-called "concealed cardiomyopathy". Only one SCA survivor had a variant identified in a channelopathy associated gene (SCN5A).
Extended molecular analysis with multi-phenotype genetic testing can identify a "concealed cardiomyopathy", and increase the diagnosis rate for clinically-idiopathic SCA survivors.
遗传性心脏病是年轻人和无缺血诱因的人发生心源性猝死（SCA）的常见原因。在这些患者中确定 SCA 的病因可进行针对性治疗和家族筛查。目前的指南建议，在怀疑存在特定遗传疾病的情况下，对 SCA 幸存者进行有限的、表型导向的基因检测，而不建议对临床特发性 SCA 幸存者进行基因检测。
研究广泛的多表型基因检测在临床特发性 SCA 幸存者中的诊断效用。
1997 年至 2019 年期间，澳大利亚悉尼的一家专门的遗传性心脏病诊所对临床特发性 SCA 幸存者进行了与心肌病或原发性心律失常综合征相关的基因分析，这些患者是经转诊至该诊所的。对临床记录进行了全面审查，根据当前的变异分类标准对基因数据进行了重新评估。
在总共 36 名临床特发性 SCA 幸存者（平均年龄 36.9±16.9 岁，61%为男性）中，有 22%（n=8）通过广泛的基因检测发现了致病变异。其中，7 种（88%）变异位于与心肌病相关的基因（ACTN2、DES、DSP、MYBPC3、MYH7、PKP2）中，尽管在发生 SCA 时心脏结构正常或结构变化亚诊断，所谓的“隐匿性心肌病”。只有一名 SCA 幸存者在与通道病相关的基因（SCN5A）中发现了变异。
多表型基因检测的扩展分子分析可以发现“隐匿性心肌病”，并提高临床特发性 SCA 幸存者的诊断率。
