Subtype
Brittle cornea syndrome (BCS)
Recessive type dominated by ocular fragility; protective eyewear is a standard management point.
| Classification | 2017 International Classification |
|---|---|
| Inheritance | autosomal recessive |
| Genes | ZNF469, PRDM5 |
| Genetic status | confirmed molecular basis |
| Prevalence | Ultra-rare |
| Distinguishing | Extreme corneal thinning and rupture risk, blue sclerae, joint hypermobility |
| Reviewed | 2026-09-16 |
Related records
Records scoped to BCS or to all EDS types.
Community venues carry a mature caution corpus — local-anesthetic duration problems, post-operative flares, and medication-sensitivity reports that predate the clinical confirmation. This layer is now partly validated (the lidocaine arc) and partly still anecdotal (medication sensitivity reports).
The 2017 classification moved EDS from a skin-and-joints frame to an explicitly multisystem one — systemic manifestations entered the hEDS criteria themselves, and companion papers covered GI, cardiovascular-autonomic, pain, and psychiatric comorbidity. This codified what patient communities had long reported.
Under the 2017 classification, definitive diagnosis of every subtype except hEDS relies on identifying a causative genetic variant. This asymmetry is the central classification problem: the most common type is the only one without a confirmatory test.
Villefranche-era "EDS type III" cohorts (1997–2017) do not map cleanly onto 2017 hEDS — the new criteria are stricter and exclude cases now filed as HSD. This index tags every record with its criteria era; meta-claims mixing eras are read with caution.
Confirmed subtype genes cluster into collagen structure (COL5A1/A2, COL3A1, COL1A1/A2, COL12A1), collagen processing (ADAMTS2, PLOD1), proteoglycan and glycosaminoglycan pathways (B4GALT7, B3GALT6, CHST14, DSE), complement (C1R, C1S), and signaling (TNXB, SLC39A13, ZNF469, PRDM5, FKBP14). The 2017 classification groups subtypes by shared pathway for research purposes.
Beighton, Solomon, and Soskolne published the nine-point articular mobility score in an Annals of the Rheumatic Diseases population study — designed for epidemiology, later adopted as the clinical hypermobility measure still used in the 2017 hEDS criteria.
The 1988 Berlin nosology for heritable connective-tissue disorders expanded EDS into eleven numbered types — a proliferation that blurred clinical boundaries and set up the later consolidation.
Beighton et al. published the revised Villefranche nosology (1997, printed 1998) consolidating EDS to six major types — classical (I/II), hypermobility (III), vascular (IV), kyphoscoliosis (VI), arthrochalasia (VIIA/B), dermatosparaxis (VIIC) — aligning clinical types with the emerging molecular era.
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.
Local anesthetic resistance — the index's reference convergence
establishedpracticestrata convergecautionPatients reported local-anesthetic failure for decades. Hakim and Grahame's 2005 survey found 58% of hypermobile patients reported inadequate anesthesia vs 21% of controls; a 2019 survey (n=988) found 88% vs 33%; in 2025 a randomized cross-over trial (n=135) confirmed shorter lidocaine duration in EDS patients. The arc — forum reports, structured survey, randomized confirmation — is the model this index exists to document.
Chopra et al.'s 2017 management paper remains the reference for EDS pain care — multimodal analgesia, physiotherapy, psychological support, and caution about long-term opioids. Evidence tiers here are low: mostly expert consensus and small series.
Tissue fragility, wound-healing complications, and — in vEDS — arterial rupture risk make surgery a deliberate decision. The 2017 orthopaedic guidance favors conservative management; the record is cautious rather than prohibitionist.
The 2021 systematic review of the EDS diagnostic journey documents protracted time-to-diagnosis, serial misdiagnosis, and healthcare dismissal across patient populations. Delay is not an anecdote — it is a measured property of the system.
The Ehlers-Danlos Society's DICE Global Registry is the central patient-powered research registry — the infrastructure behind the misdiagnosis survey and the recruitment rail for studies like HEDGE. Indexed as first-party registry infrastructure.
The ECHO program is the society's clinician-education and community-of-practice rail — how research and management knowledge reaches the providers patients actually see. Indexed as research-infrastructure, not a data source.
The federal trial registry is the canonical index of active EDS interventional and observational studies — the anesthetic-resistance RCT among them. The index's monitor tracks this portfolio for new registrations.
Orphanet (ORPHA:75531) and NIH GARD carry the reference-level disease records that anchor subtype nomenclature and prevalence estimates for rare-disease infrastructure. Indexed as reference rails rather than primary evidence.