schema: eds-research/questions/v1
questions:
  - id: heds-molecular-basis
    question: What is the molecular basis of hEDS, and how genetically heterogeneous is it?
    why_open: KLK15 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.
    status: watching
    strata_sought: [clinical, gray, registry]
    related_source_ids:
      - source-ee867f99ac8808a4ef80
      - source-daaa8e28125b9b3bb775
      - source-3440a2b9d5d99c580d3a
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"
  - id: hsd-heds-boundary
    question: Should the hEDS/HSD boundary be maintained, and how would a molecular marker change it?
    why_open: HSD 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.
    status: open
    strata_sought: [clinical, registry, community]
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"
  - id: true-prevalence
    question: What is the true prevalence of hEDS/HSD, and how much does underdiagnosis distort it?
    why_open: Textbook 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.
    status: open
    strata_sought: [clinical, registry, community]
    related_source_ids:
      - source-eaeabc3db4dd07d41bc5
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"
  - id: mcas-pots-heds-trifecta
    question: Is the hEDS-POTS-MCAS clustering a shared mechanism or a referral artifact?
    why_open: Patient 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.
    status: watching
    strata_sought: [clinical, registry, community]
    related_source_ids:
      - source-9a67b455782a95159bd9
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"
  - id: exercise-intervention-evidence
    question: Which exercise and physiotherapy modalities measurably help hEDS/HSD, and at what dose?
    why_open: PT is the mainstay recommendation but trials are small and heterogeneous; community practice runs ahead of the trial record.
    status: open
    strata_sought: [clinical, community]
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"
  - id: anesthetic-resistance-mechanism
    question: What mechanism explains reduced local-anesthetic effectiveness in EDS?
    why_open: A 2026 randomized trial supports the patient reports, but the mechanism is unexplained; hypotheses range from tissue diffusion to sodium-channel and connective-tissue effects.
    status: watching
    strata_sought: [clinical]
    related_source_ids:
      - source-ed80c4098795181b156a
      - source-99c47d7654307a3505da
      - source-27684d4afee8b83b9d25
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"
  - id: cci-tethered-cord-evidence
    question: How should craniocervical instability and tethered-cord claims in hEDS be weighed?
    why_open: These conditions come up often in patient communities, controlled evidence is limited, and surgery for them carries real risk.
    status: watching
    strata_sought: [clinical, community]
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"
  - id: diagnostic-delay-reduction
    question: Which interventions shorten the time it takes to diagnose EDS?
    why_open: The 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.
    status: open
    strata_sought: [clinical, community, registry]
    related_source_ids:
      - source-de164233cddfefc4105a
      - source-9a67b455782a95159bd9
      - source-fa671c0df94cd9c20ecb
    opened_at: "2026-09-16"
    last_reviewed: "2026-09-16"