The 2017 international classification of the Ehlers-Danlos syndromes

Fransiska Malfait (1) , Clair Francomano (2) , Peter H Byers (3) , John Belmont (4) , Britta Berglund (5) , James Black (6) , Lara Bloom , Jessica Bowen (7) , Nigel Burrows (8) , Marco Castori (9) , Helen Cohen (10) , Marina Colombi (11) , Serwet Demirdas (12) , Julie de Backer (1) , Anne de Paepe (13) , Sylvie Fournel-Gigleux (14) , Michael Bj Frank (15) , Neeti Ghali (16) , Cecilia Giunta (17) , Rodney Grahame , Alan Hakim (18) , Xavier Jeunemaitre (19) , Diana Johnson (20) , Birgit Juul-Kristensen (21) , Ines Kapferer-Seebacher (22) , Hanadi Kazkaz (23) , Tomoki Kosho (24) , Mark Lavallee , Howard Levy (25) , Roberto Mendoza-Londono (26) , Melanie Pepin (3) , F. Michael Pope (27) , Eyal Reinstein (28) , Leema Robert (29) , Marianne Rohrbach (17) , Lynn Sanders , Glenda Sobey (7) , Tim van Damme (1) , Anthony A Vandersteen (30) , Caroline van Mourik , Nicol Voermans (31) , Nigel Wheeldon , Johannes Zschocke (32) , Brad Tinkle (33)

1 Center for Medical Genetics [Ghent]
2 Johns Hopkins University and Hospital
3 Department of Pathology
4 BCM - Baylor College of Medicine
5 Karolinska Institutet [Stockholm]
6 Johns Hopkins University School of Medicine [Baltimore]
7 Sheffield Children's NHS Foundation Trust
8 Addenbrooke's Hospital
9 San Camillo Forlanini Hospital [Rome]
10 RNOH - Royal National Orthopaedic Hospital
11 UniBs - Università degli Studi di Brescia = University of Brescia
12 Erasmus MC - Erasmus University Medical Center [Rotterdam]
13 Center for Medical Genetics
14 IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire
15 CIC AP-HP (hegp Ex-Broussais)/inserm
16 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
17 University Children’s Hospital Zurich
18 Whippscross University NHS Hospital
19 Service de génétique [CHU HEGP]
20 Department of Clinical Genetics
21 SDU - University of Southern Denmark
22 Department of Operative and Restorative Dentistry
23 UCLH - University College London Hospitals
24 Shinshu University Hospital
25 JHU - Johns Hopkins University
26 SickKids - The Hospital for sick children [Toronto]
27 NPH - Northwick Park Hospital [Harrow, UK]
28 Medical Genetics Institute
29 Guy's and St Thomas' Hospital [London]
30 IWK Health Centre
31 Radboud University Medical Center [Nijmegen]
32 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
33 Children's hospital of Chicago

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.

Mots clés: collagen; classification; genetic basis; Ehlers-Danlos syndromes

Domaines: Génétique humaine

Fransiska Malfait, Clair Francomano, Peter H Byers, John Belmont, Britta Berglund, et al.. The 2017 international classification of the Ehlers-Danlos syndromes. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2017, 175 (1), pp.8 - 26. ⟨10.1002/ajmg.c.31552⟩. ⟨hal-01709259⟩