TY - JOUR
T1 - The 2017 international classification of the Ehlers–Danlos syndromes
AU - Malfait, Fransiska
AU - Francomano, Clair
AU - Byers, Peter
AU - Belmont, John
AU - Berglund, Britta
AU - Black, James
AU - Bloom, Lara
AU - Bowen, Jessica M.
AU - Brady, Angela F.
AU - Burrows, Nigel P.
AU - Castori, Marco
AU - Cohen, Helen
AU - Colombi, Marina
AU - Demirdas, Serwet
AU - De Backer, Julie
AU - De Paepe, Anne
AU - Fournel-Gigleux, Sylvie
AU - Frank, Michael
AU - Ghali, Neeti
AU - Giunta, Cecilia
AU - Grahame, Rodney
AU - Hakim, Alan
AU - Jeunemaitre, Xavier
AU - Johnson, Diana
AU - Juul-Kristensen, Birgit
AU - Kapferer-Seebacher, Ines
AU - Kazkaz, Hanadi
AU - Kosho, Tomoki
AU - Lavallee, Mark E.
AU - Levy, Howard
AU - Mendoza-Londono, Roberto
AU - Pepin, Melanie
AU - Pope, F. Michael
AU - Reinstein, Eyal
AU - Robert, Leema
AU - Rohrbach, Marianne
AU - Sanders, Lynn
AU - Sobey, Glenda J.
AU - Van Damme, Tim
AU - Vandersteen, Anthony
AU - van Mourik, Caroline
AU - Voermans, Nicol
AU - Wheeldon, Nigel
AU - Zschocke, Johannes
AU - Tinkle, Brad
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Ehlers–Danlos syndromes
KW - classification
KW - collagen
KW - genetic basis
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U2 - 10.1002/ajmg.c.31552
DO - 10.1002/ajmg.c.31552
M3 - Article
C2 - 28306229
AN - SCOPUS:85015658796
SN - 1552-4868
VL - 175
SP - 8
EP - 26
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
IS - 1
ER -