Timeline
How the idea of EDS changed over time. Each event is tagged with the diagnostic criteria in force when its sources were written, because a 1975 cohort and a 2020 hEDS cohort are not the same population.
- c. 400 BC
Early descriptions of laxity and bruising attributed to antiquity
The standard historiography (Parapia and Jackson, 2008) traces descriptions consistent with joint laxity and easy bruising to Hippocratic-era medicine. These are attributions made in hindsight: the syndrome had not been described, and no one in these accounts was diagnosed with it.
- 1682
van Meek'ren reports extraordinary skin extensibility
Amsterdam surgeon Job Janszoon van Meek'ren documented a 23-year-old patient who could pull the skin of the chest over the head. The report is commonly cited as the first detailed clinical description of the skin phenotype later associated with EDS.
- 1880s
India Rubber Men and elastic performers in travelling shows
Late nineteenth-century travelling shows featured performers whose extreme flexibility and skin elasticity were their livelihood. James Morris, who performed with Barnum and Bailey, earned $150 per week in the 1880s. Medical literature of the era (Wile 1883, Gould and Pyle 1897) documented some of them. Attributing EDS to them in hindsight is plausible for some performers and unprovable for most.
- 1892
Chernogubov presents the first modern case reports
Nikolai Chernogubov (Tschernogobow) presented two patients to the Moscow Venereology and Dermatology Society with skin fragility and hyperelasticity, joint hypermobility and luxation, and molluscoid pseudotumours. It is the first comprehensive modern case description. The syndrome is still known as Chernogubov's syndrome in Russian literature.
- 1901
Edvard Ehlers recognizes the syndrome as a distinct entity
Danish dermatologist Edvard Lauritz Ehlers published a case report of a patient with joint laxity, stretchy skin, easy bruising, frequent knee subluxations, and delayed walking. The syndrome takes part of its name from this description.
- 1908
Henri-Alexandre Danlos fixes skin extensibility and fragility as cardinal features
French physician Henri-Alexandre Danlos, working with Pautier, described the skin features that completed the syndrome's early clinical picture.
- 1936
Sack describes status dysvascularis
Georg Sack described a form with arterial rupture and organ fragility that was later formalized as the vascular type. This is the historical root of vEDS recognition.
- 1949
Johnson and Falls name the Ehlers-Danlos syndrome
The eponym joining Ehlers's and Danlos's names entered the literature in 1949, consolidating several separately described case families under one label.
- 1967
Barabas establishes heterogeneity and the arterial complication profile
A. P. Barabas demonstrated that EDS was heterogeneous and delineated the form with arterial complications, the direct ancestor of the vascular subtype (type IV in Villefranche, vEDS today).
- 1973
Beighton score published for epidemiological joint-mobility assessment
Beighton, Solomon, and Soskolne published the nine-point articular mobility score in 1973, in an Annals of the Rheumatic Diseases study of joint mobility in an African population. It was designed for epidemiology and later became the clinical measure of hypermobility used in the 2017 hEDS criteria.
- 1988
Berlin nosology expands EDS to eleven numbered types
The 1988 Berlin nosology for heritable connective-tissue disorders expanded EDS into eleven numbered types. The proliferation blurred clinical boundaries and set up the later consolidation.
- 1998
Villefranche nosology consolidates to six types
Beighton et al. published the revised Villefranche nosology (1997, printed 1998), consolidating EDS into six major types: classical (I/II), hypermobility (III), vascular (IV), kyphoscoliosis (VI), arthrochalasia (VIIA/B), and dermatosparaxis (VIIC). The revision aligned clinical types with the emerging molecular era.
- 2017-03
2017 International Classification defines thirteen subtypes
Malfait et al. and the International EDS Consortium published the current classification: thirteen subtypes, molecular confirmation required for all except hEDS, a pathogenetic scheme grouping by pathway, and the companion framework separating hEDS from HSD. Management guidelines for comorbidities accompanied the criteria for the first time.
- 2025-08
2025: KLK15 published as a candidate gene for hEDS
In August 2025 the Norris Lab and colleagues published whole-exome work in iScience implicating kallikrein (KLK) gene variants in hEDS: a recurrent KLK15 variant segregating in multiple families, rare and low-frequency variants in 14 of the 15 KLK genes, and a knock-in mouse with hEDS features in tendons and heart valves. A preprint and The Ehlers-Danlos Society's summary appeared in June 2024. The society says hEDS remains a clinical diagnosis and that replication, including in the HEDGE study, is needed.