Malfait Fransiska, Francomano Clair, Byers Peter, Belmont John, Berglund Britta, Black James, Bloom Lara, Bowen Jessica M, Brady Angela F, Burrows Nigel P, Castori Marco, Cohen Helen, Colombi Marina, Demirdas Serwet, De Backer Julie, De Paepe Anne, Fournel-Gigleux Sylvie, Frank Michael, Ghali Neeti, Giunta Cecilia, Grahame Rodney, Hakim Alan, Jeunemaitre Xavier, Johnson Diana, Juul-Kristensen Birgit, Kapferer-Seebacher Ines, Kazkaz Hanadi, Kosho Tomoki, Lavallee Mark E, Levy Howard, Mendoza-Londono Roberto, Pepin Melanie, Pope F Michael, Reinstein Eyal, Robert Leema, Rohrbach Marianne, Sanders Lynn, Sobey Glenda J, Van Damme Tim, Vandersteen Anthony, van Mourik Caroline, Voermans Nicol, Wheeldon Nigel, Zschocke Johannes, Tinkle Brad
Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552.
The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen-encoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. © 2017 Wiley Periodicals, Inc.
埃勒斯-当洛综合征（EDS）是一组临床和遗传异质性的遗传性结缔组织疾病（HCTD），其特征为关节活动过度、皮肤过度伸展和组织脆弱。在过去二十年中，划分出六个亚型的 Villefranche 分类法已被广泛用作 EDS 临床诊断的标准。对于这些亚型中的大多数，已在胶原蛋白编码基因或编码胶原蛋白修饰酶的基因中鉴定出突变。自 1998 年发表以来，已经描述了一系列新的 EDS 亚型，并在一系列新基因中鉴定出突变。国际 EDS 联盟提出了修订后的 EDS 分类，确认了 13 个亚型。对于每个亚型，我们提出了一组有助于诊断的临床标准。然而，鉴于 EDS 亚型的巨大遗传异质性和表型变异性，以及 EDS 亚型之间以及与其他 HCTD 之间的临床重叠，除活动过度型外，所有 EDS 亚型的明确诊断都依赖于通过鉴定（一个或多个）致病基因变异进行分子确认。我们还修订了活动过度型 EDS 的临床标准，以便更好地区分其他关节活动过度疾病。为满足研究需求，我们还提出了一种发病机制方案，该方案将致病蛋白在同一途径中发挥作用的 EDS 亚型重新分组。我们希望修订后的国际 EDS 分类将成为 EDS 诊断的新标准，并为未来的研究目的提供一个框架。© 2017 威利期刊公司
