The 2017 international classification of the Ehlers–Danlos syndromes

Abstract

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 collagenencoding 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.

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

“…The 13 most common, recognized EDS subtypes will be briefly discussed in this manuscript. For each subtype, major and minor criteria are proposed within the 2017 nosology, of which the major criteria involve features that occur in the majority of patients and are rather specific for that subtype, while minor criteria may overlap with other subtypes or HCTDs and might only be present in a small subset of patients (46). It is worth noting that many clinical findings show overlap between the different EDS subtypes.…”

“…In addition, a soft doughy textured skin, easy bruising, skin fragility, mulluscoid pseudotumors, subcutaneous spheroids, hernia, and epicanthal folds can be part of the phenotype, but are less specific for the classical EDS subtype or are present in only a minority of patients (46). Easy bruising during childhood is often the first presenting symptom.…”

“…Also muscle hypotonia, scoliosis, pectus deformities, osteopenia, and increased bone fragility are regularly observed and these features can also present in patients with LDS and MFS. In a minority of cases, arterial complications including rupture and dissections are reported and these cases often resemble the vEDS phenotype (46,47). Gastrointestinal symptoms are mostly observed in the hypermobile type of EDS, but are occasionally present in patients with classical EDS, and include dysphagia, reflux, constipation, and diarrhea (47).…”

A humanisation approach for the management of Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobility Type (JHS/EDS-HT)

“…Joint Hypermobility Syndrome is considered to be synonymous with EDS-hypermobility type (Grahame, 2013; Tinkle et al, 2009). An updated classification of the diagnostic criteria for the various Ehlers-Danlos syndromes has been published (Malfait et al, 2017), which includes hypermobile Ehlers-Danlos syndrome. In the medical literature it might also be referred to as Hypermobility Syndrome, but, for consistency, in this paper it will be referred to as JHS/EDS-HT.…”

“…Those with the condition report generalized joint hypermobility and symptoms like musculoskeletal complaints, recurrent joint dislocations/joint instability and chronic pain, sometimes starting in childhood (Adib, Davies, Grahame, Woo, & Murray, 2005; Clinch & Ecclestone, 2009; Malfait et al, 2017). Physiotherapy is considered to be the main mode of treatment (Simmonds & Keer, 2007), although there is little evidence relating to the success of these interventions (Palmer, Bailey, Barker, Barney, & Elliott, 2014); the reason for this is likely to be the complex individual nature of the condition.…”