Heart Rhythm Services, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada.
Cardiovascular Genetics Center, Montreal Heart Institute, Montreal, Quebec, Canada.
Can J Cardiol. 2020 Apr;36(4):584-587. doi: 10.1016/j.cjca.2019.08.041. Epub 2019 Sep 10.
Genetic testing is playing an ever-expanding role in cardiovascular care and is becoming part of the "toolkit" for the cardiovascular clinician. In patients with inherited arrhythmias, genetic testing can confirm a suspected diagnosis, establish a diagnosis in unexplained cases, and help facilitate cascade family screening. Many inherited arrhythmia syndromes are monogenic diseases arising from a single pathogenic variant involved in the structure and function of cardiac ion channels or structural proteins. As such, "arrhythmia gene panels" will often cast a wide net for such heritable diseases. However, challenges may arise when genetic testing results are ambiguous, or when genetic testing results (genotype) and clinical phenotypes do not match. In cases of "genotype-phenotype matching," genetic results complement the clinical phenotype and genetic testing can be used in diagnosis, family screening, and occasionally prognostication. It becomes more challenging when genetic results are negative or noncontributory and "contradict" the clinical phenotype. "Genotype mismatches" can also occur when genotype-positive patients have no clinical phenotype, or when genetic testing results point towards a completely different disease than the clinical phenotype. We discuss an approach to genetic testing and review the challenges that may arise when interpreting genetic testing results. Genetic testing has opened a wealth of opportunities in the diagnosis, management, and cascade screening of inherited arrhythmia syndromes, but has also opened a "Pandora's box" of challenges. Genetic results should be interpreted with caution and in a multidisciplinary clinic, with support from genetic counsellors and an expert with a focused interest in cardiovascular genetics.
基因检测在心血管护理中的作用日益扩大，正在成为心血管临床医生的“工具包”的一部分。在遗传性心律失常患者中，基因检测可以确认疑似诊断，为不明原因的病例做出诊断，并有助于进行级联家族筛查。许多遗传性心律失常综合征是由单个致病变异引起的单基因疾病，这些变异涉及心脏离子通道或结构蛋白的结构和功能。因此，“心律失常基因面板”通常会广泛检测此类遗传性疾病。然而，当基因检测结果不明确，或者基因检测结果（基因型）与临床表型不匹配时，可能会出现挑战。在“基因型-表型匹配”的情况下，基因结果补充了临床表型，基因检测可用于诊断、家族筛查，偶尔还可用于预后。当基因检测结果为阴性或无明显意义且“与”临床表型相矛盾时，情况就变得更加复杂。当基因型阳性患者没有临床表型，或者基因检测结果指向与临床表型完全不同的疾病时，也会出现“基因型不匹配”的情况。我们讨论了一种基因检测方法，并回顾了当解释基因检测结果时可能出现的挑战。基因检测为遗传性心律失常综合征的诊断、管理和级联筛查开辟了广阔的机会，但也带来了“潘多拉的盒子”般的挑战。基因检测结果应在遗传咨询师和对心血管遗传学有专业兴趣的专家的支持下，在多学科诊所中谨慎解读。
