Department of Cardiology, Inselspital, Bern University Hospital, Freiburgstrasse 8, Bern, Switzerland.
Swiss DNAlysis, Adlerstrasse 1, Dübendorf, Switzerland.
Europace. 2019 Aug 1;21(8):1145-1158. doi: 10.1093/europace/euz109.
Progressive cardiac conduction disease (PCCD) is often a primarily genetic disorder, with clinical and genetic overlaps with other inherited cardiac and metabolic diseases. A number of genes have been implicated in PCCD pathogenesis with or without structural heart disease or systemic manifestations. Precise genetic diagnosis contributes to risk stratification, better selection of specific therapy and allows familiar cascade screening. Cardiologists should be aware of the different phenotypes emerging from different gene-mutations and the potential risk of sudden cardiac death. Genetic forms of PCCD often overlap or coexist with other inherited heart diseases or manifest in the context of multisystem syndromes. Despite the significant advances in the knowledge of the genetic architecture of PCCD and overlapping diseases, in a measurable fraction of PCCD cases, including in familial clustering of disease, investigations of known cardiac disease-associated genes fail to reveal the underlying substrate, suggesting that new causal genes are yet to be discovered. Here, we provide insight into genetics and molecular mechanisms of PCCD and related diseases. We also highlight the phenotypic overlaps of PCCD with other inherited cardiac and metabolic diseases, present unmet challenges in clinical practice, and summarize the available therapeutic options for affected patients.
进行性心脏传导疾病（PCCD）通常是一种主要的遗传疾病，其临床表现和遗传背景与其他遗传性心脏和代谢疾病存在重叠。许多基因与 PCCD 的发病机制有关，无论是否存在结构性心脏病或全身表现。明确的遗传诊断有助于风险分层、选择特定治疗方法，并允许进行熟悉的级联筛查。心脏病专家应了解不同基因突变引起的不同表型以及潜在的心脏性猝死风险。遗传形式的 PCCD 常与其他遗传性心脏病重叠或并存，或在多系统综合征的背景下表现出来。尽管人们对 PCCD 及其相关疾病的遗传结构有了显著的认识，但在相当一部分 PCCD 病例中，包括疾病家族聚集性中，对已知与心脏疾病相关的基因的调查未能揭示潜在的病因，这表明新的致病基因尚未被发现。在这里，我们深入探讨了 PCCD 及相关疾病的遗传学和分子机制。我们还强调了 PCCD 与其他遗传性心脏和代谢疾病的表型重叠，提出了临床实践中的未满足的挑战，并总结了受影响患者的可用治疗选择。
