Dittmann Sven, Kerkering Janis
Institute for Genetics of Heart Diseases (IfGH) University Hospital Münster (UKM) Albert-Schweitzer-Campus 1 (Gebäude D3) 48149 Münster Germany.
Med Genet. 2025 Apr 8;37(2):125-136. doi: 10.1515/medgen-2025-2006. eCollection 2025 Jun.
Recently, cardiogenetics is a rapidly developing medical section combining cardiovascular and genetic knowledge. Inherited forms of cardiac arrhythmias are typically rare diseases (prevalence < 1:2,000) and may occur in a sporadic or familial manner, here mostly in an autosomal dominant form. They are also called "primary electrical heart disorders" due to the ECG-based diagnosis and mainly normal cardiac imaging, i.e. absence of structural heart abnormalities. Their genetic basis is heterogeneous, still incomplete (variant detection rates between 10 % and 80 %) and mostly related to cardiac ion channel genes and related regulatory units. So far, the utility of polygenic risk scores is under current evaluation. Clinical disease expressivity may range from non-penetrance to high penetrance, indicating the importance of additional clinical modifiers (genetic and non-genetic) that modulate phenotypic signs. Occurrence of symptoms, as typical for other ion channel disorders (e.g., epilepsy), also depends on exposure to specific and often genotype-related environmental triggers, that enhance the occurrence of clinically relevant and potentially life-threatening arrhythmias. In the following, the main focus is on cardiac ion channel disorders, with regard to some general genetic aspects and current guidelines indicating the value of genotyping to support early disease recognition, confirmation of diagnosis and prevention of severe cardiac events.
近年来,心脏遗传学是一个迅速发展的医学领域,它融合了心血管和遗传学知识。遗传性心律失常通常是罕见疾病(患病率<1:2000),可能以散发性或家族性方式出现,这里主要是常染色体显性遗传形式。由于基于心电图的诊断以及心脏成像基本正常,即无心脏结构异常,它们也被称为“原发性心电疾病”。其遗传基础具有异质性,仍不完整(变异检测率在10%至80%之间),且大多与心脏离子通道基因及相关调控单元有关。到目前为止,多基因风险评分的效用正在评估中。临床疾病的表现度可能从不外显到高外显,这表明了调节表型特征的其他临床修饰因子(遗传和非遗传)的重要性。症状的出现,如同其他离子通道疾病(如癫痫)一样,也取决于接触特定的、通常与基因型相关的环境触发因素,这些因素会增加临床相关且可能危及生命的心律失常的发生。接下来,主要关注心脏离子通道疾病,涉及一些一般的遗传学方面以及当前表明基因分型对支持早期疾病识别、确诊和预防严重心脏事件价值的指南。