Ehlers-Danlos syndrome, classic type, 1

Ehlers-Danlos syndrome, classic type, 1 is a connective_tissue genetic disease caused by mode of inheritance not populated in the structured source variants in COL5A1. It is not placed in the rankable burden order: only 1 of five axes are scored (cut: three of five), so the remaining 4 stay open [O], not guessed. Mechanism, scored axes, and treatment follow below.

Ehlers-Danlos syndrome, classic type, 1 is inherited as mode of inheritance not populated in the structured source and acts by haploinsufficiency ([L]). Of the five burden axes, 1 are scored (S) and 4 are open [O] (O, P, M, D); because fewer than three are scored the disease is reported as “not placed — insufficient axis coverage” (rank null), not ranked on partial data.

Gene, inheritance, and molecular mechanism

Ehlers-Danlos syndrome, classic type, 1 is inherited as not_stated [O] and is classified mechanistically as haploinsufficiency [L]. COL5A1 encodes a chain of type V collagen, which templates type I collagen fibril assembly. Haploinsufficiency yields disorganised dermal collagen fibrils.

Inheritance source: (structured MedGen field). Mechanism source: clingen:HI_score_3:2026-06-17; genes=COL5A1; PMID:10777716,10796876,8673139. These are observed, cited inputs; the classification is the reproducible analysis layer (C-D1).

In-scope clinical involvement

Classic Ehlers-Danlos syndrome combines skin hyperextensibility, atrophic cigarette-paper scarring, and generalised joint hypermobility with recurrent dislocations and easy bruising.

Organ systems [L] from HPO phenotype.hpoa v2026-06-06 (OMIM 120215,130000); P-aspect terms rolled up to HP:0000118 organ-system categories via hp.obo.

Burden axes and why this disease is not placed

For transparency the partial composite over the 1 scored axis/axes is raw_burden = 0.2500, but it is not used to rank the disease (below the ≥ 3-axis cut). The open axes (onset, progression, mortality, disability) are graded [O] with a named obstacle, never imputed.

The natural-history registry passes lift onset (Orphanet, R6) and disability (GBD 2013 disability weights, R7) to registry [L] where an entity-anchored mapping exists, lift severity (HPO Severity-modifier subtree, R8) where the dominant sequela is annotated, and lift progression (curated PMC open-access literature with a frozen-R3-derived tier, R9) where a cited disease-level magnitude for the dominant untreated sequela exists. For some diseases the added disability axis was enough to cross the ≥ 3-axis cut and enter the placed residual order; for this one it was not — and its dominant sequela carries no open HPO severity annotation, so no registry severity tier is available (the open HPO severity annotations elsewhere are feature-level; the OMIM clinical synopsis, the disease-level alternative, is API-key-gated and the key is unobtainable for an individual researcher). Scoring three or more axes at registry grade (via published functional & survival literature) would let this disease enter the rankable residual order; until then it is reported here, never imputed.

Established treatment

The established disease-directed approach is supportive: skin and joint protection, wound care; no disease-modifying therapy. Mechanistically: supportive only [L]. Its effect on natural history is classified symptomatic (efficacy offset e = 0.1000, residual factor R_treat = 0.9000); this offset would apply to the burden score once the disease is placed.

Evidence tier: accession-dated to the GeneReviews NBK1244 Management section [L] (initial posting May 29, 2007; last revision February 1, 2024; retrieved 2026-06-18; corroborating term(s): “skin, joint, wound”).