Research program
What the index is tracking: open questions, the searches it uses to find new evidence, and a log of every change to the data.
Open questions
Questions the evidence has not settled, with the kinds of evidence that could answer each.
What is the molecular basis of hEDS, and how genetically heterogeneous is it?
watchingKLK15 is a candidate gene that is not yet used for diagnosis, and the HEDGE study (1,000 people with hEDS) is expected to report further genetic findings. hEDS remains a clinical diagnosis.
Should the hEDS/HSD boundary be maintained, and how would a molecular marker change it?
openHSD was defined as a residual category in 2017; patients excluded by strict hEDS criteria may share the same biology. The criteria review study is active.
What is the true prevalence of hEDS/HSD, and how much does underdiagnosis distort it?
openTextbook figures (1 in 5,000) conflict with diagnosed-prevalence data (about 1 in 500 in Wales) and community estimates are higher still. Ascertainment bias runs in both directions.
Is the hEDS-POTS-MCAS clustering a shared mechanism or a referral artifact?
watchingPatient communities report the triad often, and POTS and MCAS were among the diagnoses most often endorsed in a registry survey, but evidence on mechanism is thin and the diagnostic criteria for each condition differ in rigor.
Which exercise and physiotherapy modalities measurably help hEDS/HSD, and at what dose?
openPT is the mainstay recommendation but trials are small and heterogeneous; community practice runs ahead of the trial record.
What mechanism explains reduced local-anesthetic effectiveness in EDS?
watchingA 2026 randomized trial supports the patient reports, but the mechanism is unexplained; hypotheses range from tissue diffusion to sodium-channel and connective-tissue effects.
How should craniocervical instability and tethered-cord claims in hEDS be weighed?
watchingThese conditions come up often in patient communities, controlled evidence is limited, and surgery for them carries real risk.
Which interventions shorten the time it takes to diagnose EDS?
openThe average time to diagnosis was 10.39 years in a Global Registry survey of people with hEDS, and the median was 23.0 years for hEDS or HSD at one German clinic. Clinician education programs such as EDS ECHO exist, but evidence on whether they shorten diagnosis is early.
Collections
Where kinds of evidence agree
Records where independent studies or reports from more than one kind of evidence point the same way.
The hEDS genetics frontier
The search for hEDS molecular markers, from unknown status to KLK15 and HEDGE.
The diagnostic odyssey
Quantified delay, misdiagnosis, and dismissal across clinical and registry evidence.
Searches for new evidence
Each search, what it looks for, how often it should run, and when it was last checked. Nothing runs these searches automatically.
PubMed Ehlers-Danlos latest
activeNew peer-reviewed EDS literature across all subtypes and comorbidity domains.
PubMed hypermobility spectrum latest
activeHSD literature that borders or feeds the hEDS corpus.
ClinicalTrials.gov EDS condition search
activeNew and updated interventional and observational trials in EDS.
Ehlers-Danlos Society research news
activeRegistry reports, HEDGE milestones, funded-study announcements, guideline updates.
HEDGE study publication watch
activeFirst HEDGE publications were expected late 2025 into 2026; watch for genetic-marker findings.
Public community venue signal scan
activeRecurring practice and comorbidity signals reported by patients; never individual posters.
Preprint servers EDS watch
activeGenetics and biomarker preprints ahead of peer review (e.g., KLK15 lineage).
International Consortium and guideline watch
activeCriteria revision proposals, management guideline updates, pediatric framework follow-ups.
Historical archive sweep
activePre-nosology case descriptions and documented folk management of joint laxity.
Change log
Every update to the data, oldest first. Corrections add a new entry; earlier entries are not edited.
Subtype wording and one record page description, checked against the sources each subtype already lists
Wording and data corrections only. No record ID, source, tier, or citation changed. Drafted by an AI agent (Claude Code) during the 2026-09-28 search and copy pass; no independent human review is recorded.
- hist-barabas-1967-vascular: Added a page description. The first summary sentence is longer than 160 characters, and the page description had been cut to "A. P." at the initials. The description restates facts already in the record.
- subtypes.yml veds: Summary rewritten in plain words. It names the organs the 2017 classification lists for rupture (arteries, bowel, uterus) and drops the phrase "celiprolol debate", which the page did not explain or cite.
- subtypes.yml veds: Prevalence changed from "Estimated around 1 in 50,000 to 1 in 200,000" to "Rare". Neither listed source states that range. The National Academies EDS chapter (NBK584966) gives 1 in 50,000 while citing another work, and The Ehlers-Danlos Society's EDS types page gives no figure.
- subtypes.yml heds: Prevalence now gives the 2019 Wales figure with its value and population (194.2 per 100,000 in 2016/2017, EDS and joint hypermobility syndrome combined) and drops the "older textbook figures near 1 in 5,000", which no listed source reports as a result.
Plain-language wording on public pages and in the collections catalog
Copy-only correction. No record, source, tier, or citation changed.
- diagnostic-odyssey-evidence: Collection description now says "clinical and registry evidence" instead of "clinical and registry strata", keeping the internal word off the public page.
Citation, evidence-label, and number corrections after resolving every cited DOI and PMID
Every DOI and PMID in the source catalog was resolved against PubMed, Crossref, and Europe PMC on 2026-09-23, and the resolved title, venue, and year were compared with the catalog entry. Record IDs are unchanged; corrected source IDs are re-derived from their URLs and dates. Drafted by an AI agent (Claude Code) during the 2026-09-23 editorial pass; no independent human review is recorded.
- source-aef7c864eb540644a26f: Replaced by source-99c47d7654307a3505da. The link pointed to PMID 15684371 ("Appendicitis after appendicectomy"); the Hakim et al. letter is PMID 15684369. Tier cohort-study changed to cross-sectional-study.
- source-8cddcecd9d7a698123e5: Replaced by source-0bcf3a495f5d5a3f3899. PMID 4259630 is a 1972 cartilage paper (Bjelle et al.); Beighton, Solomon, and Soskolne 1973 is PMID 4751776. Tier cohort-study changed to cross-sectional-study.
- source-328501b217c2b3d0d2d2: Title corrected. DOI 10.1002/ajmg.c.31545 is Engelbert et al.'s physical therapy paper, not Chopra et al.'s pain paper. The ID is unchanged because the URL and date are unchanged.
- source-d7ba05272083315d9e1f: Added Chopra et al., Pain management in the Ehlers-Danlos syndromes (10.1002/ajmg.c.31554), now cited by mgmt-pain-management-2017.
- source-5a8d9db9800230d918cf: Replaced by source-1dfb4ae3ff5aafdd0577. https://www.ehlers-danlos.com/registry/ returns 404; the DICE registry page is /eds-global-registry/. The venue-dice-registry URL was updated to match.
- source-d91980e8e90850a3f3b9: Replaced by source-ed80c4098795181b156a. Publication date 2025 changed to 2026-03. Note restated from the abstract; "confirming decades of patient reports" removed.
- source-d4a910b62f451448889e: Replaced by source-9a67b455782a95159bd9. Publication year 2024 changed to 2023 and publisher PMC to Genetics in Medicine Open. Note restated from the abstract.
- source-3dd9471fb00916c6141b: Replaced by source-fd495bad5265f19454c2. Publication year 1979 changed to 1978; publisher PubMed changed to The Journal of Rheumatology.
- source-21337422dde3976b584c: Tier cohort-study changed to qualitative-study; publisher BMJ changed to BMJ Connections Clinical Genetics and Genomics.
- source-27684d4afee8b83b9d25, source-8d222b21a7423563aba4, source-de164233cddfefc4105a: Tier cohort-study changed to cross-sectional-study for these three surveys. Notes restated from the papers. The German 22-year figure is the overall median (mean 22.9 years); the hEDS/HSD median is 23.0 years. The paper's abstract calls these medians means; its Table 2 and discussion give them as medians with interquartile ranges. The Australian 10 to 12 years is a support-group estimate quoted in the paper's introduction.
- source-fa671c0df94cd9c20ecb, source-be972ed50decef4cbf0b: Publishers corrected from PubMed and NCBI Bookshelf to the Journal of the American Association of Nurse Practitioners and the National Academies Press (chapter 4 of the 2022 report).
- public/research/sources.yml, public/research/venues.yml: Removed unsourced claims that Inspire, r/ehlersdanlos, and The Ehlers-Danlos Society are the largest of their kind, and the unverified member count for r/ehlersdanlos.
- mgmt-pt-mainstay: Tier for source-328501b217c2b3d0d2d2 changed from consensus-statement to its catalog tier, expert-review. Status established changed to probable, since no remaining attestation meets the established rule.
- mgmt-pain-management-2017: Now cites the Chopra paper instead of the physical therapy paper. Summary restated from the Chopra abstract; the claims about opioid caution, psychological support, and being the reference for pain care were removed because the abstract does not support them.
- mgmt-lidocaine-resistance: Trial date changed to 2026-03. Survey tiers changed to cross-sectional-study. Summary restated from the papers, and "for decades" removed. The risk note now attributes its advice to the trial authors.
- px-trauma-informed-2025: Tier changed to qualitative-study and status established to probable. Journal named correctly. The sample size (n=9) and the quoted phrase could not be confirmed from the abstract and were removed.
- px-german-cohort-manifestations: n=105 and "diagnosed 2021 to 2024" corrected to 99 respondents (80 with hEDS or HSD) at the Cologne clinic, surveyed December 2021 to May 2023. Symptoms restated from the full text. Tier changed to cross-sectional-study and status established to probable.
- px-diagnostic-odyssey-2021: Summary restated from the sources with each population named. "22-year median for hEDS/HSD" corrected to a median of 23.0 years for hEDS/HSD (22.0 is the median for all respondents); the Australian 10 to 12 year figure removed as a support-group estimate.
- com-misdiagnosis-load: Date 2024 changed to 2023. Status established changed to probable after the qualitative source was relabeled.
- com-trifecta-pattern, com-cci-tethered-cord: Removed unsourced claims that patient communities named the triad before clinical reviews and that surgical case series support CCI and tethered-cord claims. Registry wording matched to the survey.
- hist-van-meekren-1682, hist-ehlers-1901, hist-danlos-1908, hist-early-circus-performers, folk-performer-training: Attestations of the 2008 Parapia and Jackson review changed from primary-historical-document or contemporaneous-clinical-account to its catalog tier, retrospective-account.
- hist-van-meekren-1682: Removed the citation of Denko's 1978 translation, which translates Chernogubov's 1892 reports and is not a primary document for the 1682 case.
- signal-subluxation-load: Attestation of the Ben's Friends venue changed from patient-org-synthesis to its catalog tier, single-venue-pattern.
- hist-sack-1936-dysvascularis, hist-barabas-1967-vascular: Removed the attestation of the National Academies chapter, which does not mention Sack or Barabas, and with it the convergent label.
- hist-named-ehlers-danlos-1949: Marked refuted. The National Academies chapter it cites credits Johnson and Falls (1949) with the first report of autosomal-dominant inheritance and cites Ronchese's 1936 paper on "the so-called Ehlers-Danlos syndrome", so the name was in use before 1949.
- hist-danlos-1908: Removed the claim that Danlos's own case was likely pseudoxanthoma elasticum; neither cited source supports it.
- hist-berlin-1988: Marked contested. The record says the 1988 nosology had eleven types; the National Academies chapter it cites says nine. Not resolved in this run.
- gen-klk15-first-candidate, hist-klk15-2025, gen-hedge-study, hist-chernogubov-1892, hist-ehlers-1901, hist-danlos-1908, hist-international-2017, class-heds-2017-criteria: Corroboration convergent changed to single-origin. In each record the strata restate one study, one program's own pages, one classification, or one historical report, so they do not corroborate each other.
- gen-klk15-first-candidate, hist-klk15-2025, subtypes.yml heds, questions.yml heds-molecular-basis: Removed claims that KLK15 is the first gene associated with hEDS; neither the paper nor the society's summary says so. KLK15 is described as a candidate gene.
- hist-beighton-score-1973: Source tier changed to cross-sectional-study. Added the 2017 classification as the source for the use of the Beighton score in the hEDS criteria.
- cross-stratum-convergences: Removed hist-early-circus-performers, which cites one stratum and carries no corroboration.
- subtypes.yml hsd: Prevalence no longer says HSD is more common than hEDS by definition; it gives the 2019 Wales figure for EDS and joint hypermobility syndrome combined.
- prog-dice-registry: Replaced the claim that the registry is a recruitment rail for HEDGE with what the 2023 survey paper reports, that its respondents were registry members also enrolled in HEDGE.
- questions.yml diagnostic-delay-reduction: The claim that delays of 10 to 22 years are documented across cohorts was replaced with the registry survey's average and the German clinic's median, with their populations.
- com-multisystem-2017: Removed the claim that systemic manifestations such as digestive, autonomic, and fatigue problems entered the 2017 hEDS criteria, and the unsourced claim that the criteria codified patient reports. The criteria's systemic features (Feature A) are connective-tissue signs; chronic musculoskeletal pain counts under Feature C. Added the Chopra pain review as a source for the companion-paper sentence.
- px-fatigue-underrecognized: Removed the unsourced claims that fatigue was systematically underweighted and that the 2017 criteria restored it to the clinical picture. The summary now gives the German survey figure for fatigue.
- gen-hedge-study: The claim that HEDGE is the largest dedicated hEDS genetics effort was removed as unsourced; the society's October 2025 timeline is quoted with its caveat that timelines may shift.
- public/research/publication-policy.yml: Policy rule texts restated in plain words. The corroboration rule now names single-origin, the state added in this run; the ledger rule now says a wrong record is marked refuted rather than silently rewritten.
- gen-collagen-and-pathway-map: Gene groups rebuilt from the 2017 classification's pathogenetic scheme. The record had placed PLOD1 under collagen processing, COL12A1 under collagen structure, and TNXB, FKBP14, SLC39A13, ZNF469, and PRDM5 under a "signaling" group the classification does not have.
- dx-heds-remains-clinical: The society's position is quoted as it states it (further studies are needed to replicate the finding), rather than as a condition for ending clinical diagnosis.
- 23 records in the corpus: Added a page description to each record whose first summary sentence is longer than 160 characters, restating facts already in the record.
- all corpus files, collections.yml, questions.yml, venues.yml: Titles, summaries, notes, and category descriptions edited for plain language without changing their claims. Em dashes, title epithets, and clauses describing how the index files a record were removed. Claims that changed are listed in the entries above.
Initial corpus bootstrap across all five strata
Seeded the classification, genetics, diagnostic-journey, management, community, historiography, and folk-practice categories with primary-linked records. Lidocaine resistance admitted as the reference convergent record; KLK15 admitted as emerging pending HEDGE replication.