Hypohidrotic Ectodermal Dysplasias (HED)

name: Hypohidrotic Ectodermal Dysplasias
display_name: Hypohidrotic Ectodermal Dysplasias (HED)
creation_date: "2026-06-14T00:00:00Z"
description: >-
  A curated grouping of explicit hypohidrotic ectodermal dysplasia disease
  entries caused by defects in the EDA-EDAR-EDARADD-NF-kappaB signaling axis.
  Members share impaired ectodermal appendage morphogenesis, especially eccrine
  sweat-gland, hair-follicle, and tooth development, producing the classic HED
  triad of hypohidrosis, sparse hair, and hypodontia or oligodontia with
  variably conical teeth.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PATHWAY
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped as an explicit curated union of HED entries that perturb the
  ectodysplasin ligand-receptor-adaptor pathway, not as all ectodermal
  dysplasias. The current KB contains standalone EDA-, EDAR-, and
  EDARADD-related HED entries with different inheritance patterns and molecular
  lesions but a shared developmental pathway and cardinal clinical triad. The
  grouping keeps these disease entries separate because ligand deficiency,
  receptor dysfunction, and adaptor defects differ in inheritance, prevalence,
  variant mechanism, and therapeutic implications. Future batches can add
  WNT10A-related HED or other explicit HED entries when standalone Disease
  entries are curated.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0016535
      label: hypohidrotic ectodermal dysplasia
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      closeMatch: the grouping corresponds to the MONDO hypohidrotic
      ectodermal dysplasia class but is implemented as an explicit curated
      subset of current dismech Disease entries rather than as an automatic
      ontology closure over every HED-related subtype.
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        Listed members are the current KB's EDA-, EDAR-, and EDARADD-related
        HED entries. Additional MONDO HED descendants should be added only when
        standalone Disease entries are curated.
membership_criteria:
- description: >-
    A member is an explicit hypohidrotic ectodermal dysplasia Disease entry
    involving reduced EDA/EDAR/EDARADD-dependent canonical NF-kappaB signaling
    and at least one cardinal HED phenotype, such as hypohidrosis, sparse hair,
    hypodontia, oligodontia, or conical teeth.
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Involves canonical NF-kappaB signaling downstream of the EDA pathway.
      biological_processes:
      - preferred_term: canonical NF-kappaB signal transduction
        term:
          id: GO:0007249
          label: canonical NF-kappaB signal transduction
    - operator: OR
      description: Has a cardinal HED sweat, hair, or tooth phenotype.
      operands:
      - criterion_predicate: HAS_PHENOTYPE
        description: Hypohidrosis.
        phenotype_term:
          preferred_term: Hypohidrosis
          term:
            id: HP:0000966
            label: Hypohidrosis
      - criterion_predicate: HAS_PHENOTYPE
        description: Sparse hair.
        phenotype_term:
          preferred_term: Sparse hair
          term:
            id: HP:0008070
            label: Sparse hair
      - criterion_predicate: HAS_PHENOTYPE
        description: Hypodontia.
        phenotype_term:
          preferred_term: Hypodontia
          term:
            id: HP:0000668
            label: Hypodontia
      - criterion_predicate: HAS_PHENOTYPE
        description: Oligodontia.
        phenotype_term:
          preferred_term: Oligodontia
          term:
            id: HP:0000677
            label: Oligodontia
      - criterion_predicate: HAS_PHENOTYPE
        description: Conical tooth.
        phenotype_term:
          preferred_term: Conical tooth
          term:
            id: HP:0000698
            label: Conical tooth
      - criterion_predicate: HAS_PHENOTYPE
        description: Small, conical teeth.
        phenotype_term:
          preferred_term: Small, conical teeth
          term:
            id: HP:0200141
            label: Small, conical teeth
members:
- member: X-linked Hypohidrotic Ectodermal Dysplasia
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      EDA loss-of-function disrupts the ectodysplasin A ligand, preventing
      normal EDAR activation and downstream NF-kappaB signaling during
      ectodermal appendage induction. This X-linked recessive form is the most
      common HED subtype and produces hypohidrosis, sparse hair, oligodontia,
      conical teeth, and thermoregulation risk.
    gene:
      preferred_term: EDA
      term:
        id: hgnc:3157
        label: EDA
- member: EDAR-Related Hypohidrotic Ectodermal Dysplasia
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      EDAR variants impair the ectodysplasin A receptor, reducing ligand
      binding, receptor signaling, or EDARADD recruitment. EDAR-related HED can
      be autosomal recessive or autosomal dominant and is differentiated from
      EDA-related disease by receptor-level disruption of the same pathway.
    gene:
      preferred_term: EDAR
      term:
        id: hgnc:2895
        label: EDAR
- member: EDARADD-Related Hypohidrotic Ectodermal Dysplasia
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      EDARADD biallelic loss-of-function disrupts the intracellular adaptor
      connecting EDAR to TRAF6/IKK/NF-kappaB activation, producing autosomal
      recessive HED with the same sweat-gland, hair, and tooth developmental
      failure through an adaptor-level lesion.
    gene:
      preferred_term: EDARADD
      term:
        id: hgnc:14341
        label: EDARADD
notes: >-
  Exclude broad ectodermal dysplasia entries and syndromic entities such as
  TP63 ectodermal dysplasia spectrum, IKBKG-related immunodeficiency with or
  without ectodermal dysplasia, ectodermal dysplasia and immunodeficiency 2,
  KRT85 hair/nail ectodermal dysplasia, focal dermal hypoplasia, and acquired
  ectodermal abnormalities unless the standalone Disease entry is explicitly
  curated as hypohidrotic ectodermal dysplasia. WNT10A-related HED is a
  high-value future member once represented by a standalone Disease entry.