The 2017 international classification of the Ehlers–Danlos syndromes

  title={The 2017 international classification of the Ehlers–Danlos syndromes},
  author={Fransiska Malfait and Clair A Francomano and Peter H Byers and John W. Belmont and Britta Berglund and James Black and Lara Bloom and Jessica M. Bowen and Angela F Brady and Nigel P. Burrows and Marco Castori and Helen Cohen and Marina Colombi and Serwet Demirdas and Julie De Backer and Anne De Paepe and Sylvie Fournel‐Gigleux and Michael Frank and Neeti Ghali and Cecilia Giunta and Rodney Grahame and Alan J Hakim and Xavier Jeunema{\^i}tre and Diana S. Johnson and Birgit Juul-Kristensen and Ines Kapferer-Seebacher and Hanadi Kazkaz and Tomoki Kosho and Mark E. Lavallee and Howard P. Levy and Roberto Mendoza-Londono and Melanie G Pepin and F. Michael Pope and E Reinstein and Leema Robert and Marianne Rohrbach and Lynn S Sanders and Glenda J. Sobey and Tim Van Damme and Anthony Vandersteen and Caroline van Mourik and Nicol C. Voermans and Nigel M. Wheeldon and Johannes Zschocke and Brad T Tinkle},
  journal={American Journal of Medical Genetics Part C: Seminars in Medical Genetics},
  pages={26 - 8}
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… 

Biomarkers for Ehlers-Danlos Syndromes: There Is a Role?

This review focused on the study of two of the most common forms of EDS—classic and hypermobile—by trying to identify possible biomarkers that could be of great help to confirm patients’ diagnosis and their follow up.

Molecular Genetics and Pathogenesis of Ehlers–Danlos Syndrome and Related Connective Tissue Disorders

Different clinical, genetic and molecular aspects of several EDS subtypes and some related disorders are focused on, offering novel findings and future research and nosological perspectives.

Understanding the basis of Ehlers–Danlos syndrome in the era of the next-generation sequencing

This review summarizes the contribution of NGS technologies to the current knowledge of the genetic background in different EDS subtypes and identifies the genetic bases of unresolved EDS types and support clinical counseling.

Diagnostic outcomes for molecular genetic testing in children with suspected Ehlers–Danlos syndrome

There is a correlation between generalized joint hypermobility, poor healing, easy bruising, atrophic scars, skin hyperextensibility, and developmental dysplasia of the hip with a positive molecular result.

Ehlers-Danlos syndromes and epilepsy: An updated review

Hypermobile Ehlers‐Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes

In this review, the current molecular, genetic, epidemiologic, and pathogenetic findings related to EDS are summarized with a focus on the hypermobile type.

Classification, nosology and diagnostics of Ehlers-Danlos syndrome

  • B. Hamel
  • Medicine
    Journal of Biomedicine and Translational Research
  • 2019
The frequent types of EDS can be diagnosed after careful history taking and clinical examination, but for definite diagnosis molecular confirmation is needed in all types.

A pole of competence for Ehlers–Danlos syndromes

  • M. Enjalbert
  • Medicine
    Annals of Physical and Rehabilitation Medicine
  • 2018

The Ehlers–Danlos syndromes

The epidemiology, mechanisms, diagnosis and treatment of these syndromes are discussed, with common features including joint hypermobility, soft and hyperextensible skin, abnormal wound healing and easy bruising.

[Up-to-date classification and multidisciplinary symptoms of Ehlers-Danlos syndromes].

The clinical aspects of the novel classification of Ehlers-Danlos syndrome are summarized, which is a group of rare, hereditary connective tissue disorders, which displays a high clinical and genetic heterogeneity and harbors many multidisciplinary properties.



Ehlers‐Danlos syndromes: Revised nosology, Villefranche, 1997

This work proposes a revision of the classification of the Ehlers-Danlos syndromes based primarily on the cause of each type based on major and minor diagnostic criteria defined for each type and complemented whenever possible with laboratory findings.

Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK).

This work proposes a revision of the classification of the Ehlers-Danlos syndromes based primarily on the cause of each type based on major and minor diagnostic criteria defined for each type and complemented whenever possible with laboratory findings.

Clinical and molecular characterization of 40 patients with classic Ehlers–Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations

The findings highlight that the three major criteria for c EDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients and confirm that COL5A1 andCOL5A2 are the major, if not the only, genes involved in cEDs.

A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.

This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the Ehlers-Danlos syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix.

Targeted next-generation sequencing makes new molecular diagnoses and expands genotype–phenotype relationship in Ehlers–Danlos syndrome

Unbiased NGS-based sequencing made new molecular diagnoses outside the expected EDS genotype–phenotype relationship and identified previously undetected clinically actionable variants in aortopathy susceptibility genes.

A large duplication in the gene for lysyl hydroxylase accounts for the type VI variant of Ehlers-Danlos syndrome in two siblings.

The data indicate that the mRNA for lysyl hydroxylase produced in the affected cells is about 4 kb in size, whereas it is 3.2 kb in the control cells, and an apparently homozygous duplication rearrangement of nucleotides 1176 to 1955, corresponding to amino acids 326 to 585 in the normal sequence.

Echocardiographic findings in classical and hypermobile Ehlers–Danlos syndromes

The “pouching” shape of the SV was more common in hypermobile type than in the classical type of EDS, and 26/38 subjects demonstrated a prominent right coronary artery easily visualized by trans‐thoracic echocardiography, and 10/38 had an elongated cardiac silhouette on the 4‐chamber apical views.

Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria

Overall, over 90% of patients fulfilling all major Villefranche criteria for classic EDS were shown to harbor a type V collagen defect, which indicates that this is the major—if not only—cause ofclassic EDS.