Neural Crest Melanocyte Deficiency Disorders

name: Neural Crest Melanocyte Deficiency Disorders
display_name: Neural Crest Melanocyte Deficiency Disorders
creation_date: "2026-06-18T00:00:00Z"
description: >-
  Neural crest melanocyte deficiency disorders are Waardenburg-spectrum
  neurocristopathies in which upstream transcriptional or endothelin signaling
  lesions impair melanoblast migration, survival, or differentiation. The
  shared downstream consequence is reduced melanocytes in auditory and
  pigmentary tissues, producing sensorineural hearing impairment and pigmentary
  abnormalities, with enteric or glial involvement determined by the gene axis.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PATHWAY
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on a shared neural-crest melanocyte developmental mechanism: each
  member conforms to the neural_crest_melanocyte_deficiency module. The members
  are kept separate because EDN3/EDNRB disease primarily disrupts endothelin
  ligand-receptor signaling in melanoblast and enteric neural crest migration,
  whereas SOX10 disease disrupts a transcription-factor axis affecting
  melanocyte, enteric, Schwann-cell, and oligodendrocyte development.
membership_criteria:
- description: >-
    A disorder belongs to this grouping if and only if it conforms to the neural
    crest melanocyte deficiency module, linking a neural-crest developmental
    lesion to melanoblast migration/survival failure and auditory-pigmentary
    disease.
  criteria_semantics: NECESSARY_AND_SUFFICIENT
  logic:
    criterion_predicate: CONFORMS_TO_MODULE
    module: neural_crest_melanocyte_deficiency
    description: >-
      Conforms to the neural crest melanocyte deficiency module.
members:
- member: EDN3/EDNRB Waardenburg-Shah
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      EDN3 ligand or EDNRB receptor loss impairs endothelin signaling during
      melanoblast and enteric neural crest migration, distinguishing this
      member by prominent Hirschsprung disease with auditory-pigmentary
      Waardenburg features.
    gene:
      preferred_term: EDNRB
      term:
        id: hgnc:3180
        label: EDNRB
- member: SOX10 Neurocristopathy Spectrum
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      SOX10 disruption impairs a neural crest and glial transcriptional program
      upstream of MITF, producing auditory-pigmentary Waardenburg disease with
      variable enteric aganglionosis, peripheral neuropathy, and central
      dysmyelination across the spectrum.
    gene:
      preferred_term: SOX10
      term:
        id: hgnc:11190
        label: SOX10
notes: >-
  Two-member grouping over existing module-conforming entries. Additional
  Waardenburg-spectrum entries can be added when they declare conformance to
  the neural crest melanocyte deficiency module.