Paul M, Schulze-Bahr E, Breithardt G, Wichter T
Universitätsklinikum Münster, Medizinische Klinik und Poliklinik C-Kardiologie und Angiologie, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany.
Z Kardiol. 2003 Feb;92(2):128-36. doi: 10.1007/s00392-003-0892-9.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disorder of unknown origin. In recent years, the disease has been recognized as a major cause of ventricular tachyarrhythmias and sudden cardiac death in young patients with apparently normal hearts. Although characteristic structural, imaging and electrocardiographic features are included in a proposed catalogue of diagnostic criteria, the correct diagnosis of ARVC often remains difficult. Much effort has been undertaken to enlarge the knowledge on pathophysiological mechanisms of the disease. The role of molecular genetics for the pathogenesis of ARVC is discussed in the following review. On the basis of linkage analyses in large families affected by ARVC, there is growing evidence for genetic alterations in ARVC, which, in the majority of chromosomal loci (seven) reported so far, follow a Mendelian autosomal-dominant pattern of inheritance with variable penetrance and polymorphic phenotype. Besides this, two autosomal-recessive forms of ARVC are known. These can be differentiated from the autosomal-dominant forms not only in terms of the mode of inheritance but also as to their specific phenotype: patients with Naxos disease exhibit characteristic hair and skin abnormalities and experience a more severe course of disease. Patients with another autosomal-recessive form display the typical but milder signs of ARVC together with opacifications of the crystalline lens. So far, two mutations in cardiac genes responsible for the development of ARVC have been reported. A homozygous two base pair deletion in the gene encoding for the cytoskeletal protein plakoglobin seems to account for the evolution of Naxos disease. The second mutation affecting the cardiac ryanodine receptor gene was found in patients with ARVC-2. Routine genetic testing of patients or relatives with a suspected diagnosis of ARVC is not available at present but may become the future gold standard with potential implications for a better understanding of the pathogenesis and management of the disease.
致心律失常性右室心肌病（ARVC）是一种病因不明的原发性心肌疾病。近年来，该疾病已被公认为是心脏看似正常的年轻患者发生室性快速心律失常和心源性猝死的主要原因。尽管拟议的诊断标准目录中包含了特征性的结构、影像学和心电图特征，但ARVC的正确诊断往往仍然困难。人们已经付出了很多努力来扩大对该疾病病理生理机制的认识。以下综述将讨论分子遗传学在ARVC发病机制中的作用。基于对受ARVC影响的大家族进行的连锁分析，越来越多的证据表明ARVC存在基因改变，在迄今为止报道的大多数染色体位点（七个）中，其遵循孟德尔常染色体显性遗传模式，具有可变的外显率和多态性表型。除此之外，已知还有两种常染色体隐性形式的ARVC。这些不仅可以根据遗传方式与常染色体显性形式区分开来，而且在其特定表型方面也有所不同：纳克索斯病患者表现出特征性的毛发和皮肤异常，并且病程更为严重。另一种常染色体隐性形式的患者表现出典型但较轻的ARVC体征以及晶状体混浊。迄今为止，已经报道了两种与ARVC发生相关的心脏基因突变。编码细胞骨架蛋白桥粒斑珠蛋白的基因中一个纯合的两个碱基对缺失似乎是纳克索斯病演变的原因。在ARVC - 2患者中发现了影响心脏雷诺丁受体基因的第二个突变。目前尚无法对疑似ARVC诊断的患者或亲属进行常规基因检测，但这可能会成为未来的金标准，对更好地理解该疾病的发病机制和治疗具有潜在意义。
