Disorders of Gonadal Development (Gonadal Dysgenesis and Sex Reversal)

name: Gonadal Dysgenesis
display_name: Disorders of Gonadal Development (Gonadal Dysgenesis and Sex Reversal)
creation_date: "2026-06-13T00:00:00Z"
description: >-
  A group of disorders of sex development arising at the level of gonadal
  determination — the embryonic switch that commits the bipotential gonad to
  testis or ovary. Defects in the testis-determination pathway (or its ectopic
  activation) uncouple gonadal sex from chromosomal sex, producing streak gonads
  or sex reversal: a 46,XY individual who fails to form testes, or a 46,XX
  individual who forms testes. This is the gonadal-determination subset of the
  broader DSD classification, kept distinct from disorders of androgen synthesis
  or action, which act downstream of an already-determined gonad.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PATHWAY
grouping_rationale: >-
  Grouped on a shared developmental mechanism: each member is a defect of gonadal
  determination/sex determination, and each declares the gonad development
  and/or sex determination biological process. Members are kept as separate
  Disease entries because they differ in karyotype and in the direction of the
  determination defect (failure of testis formation in 46,XY gonadal dysgenesis,
  failure of ovary formation in 46,XX gonadal dysgenesis, ectopic testis
  formation in 46,XX testicular DSD). The criteria are NECESSARY: a gonad-
  development/sex-determination lesion is entailed by membership and is used to
  audit members, but is not asserted as sufficient. This grouping deliberately
  narrows the previously over-broad "Disorders of Sex Development" union to its
  mechanistically coherent gonadal-determination core.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0001967
      label: gonadal dysgenesis
    mapping_predicate: skos:broadMatch
    mapping_source: MONDO
    mapping_justification: >-
      broadMatch rather than closeMatch: this grouping (display name "Disorders of
      Gonadal Development — Gonadal Dysgenesis and Sex Reversal") is broader than
      MONDO:0001967 (gonadal dysgenesis), because it also includes 46,XX
      testicular DSD (MONDO:0100249) — a sex-reversal disorder with a determined
      (not dysgenetic) gonad that MONDO classifies under DSD rather than gonadal
      dysgenesis.
    consistency:
    - reference: MONDO
      consistent: INCONSISTENT
      notes: >-
        2/3 listed members are is-a descendants of MONDO:0001967; 46,XX
        testicular DSD (MONDO:0100249) is a determination/sex-reversal disorder
        outside the gonadal-dysgenesis subtree, making the grouping broader than
        the MONDO class.
membership_criteria:
- description: >-
    A member perturbs gonadal determination — it declares the gonad development
    process and/or the sex determination process.
  criteria_semantics: NECESSARY
  logic:
    operator: OR
    description: >-
      Involves gonad development and/or sex determination (the gonadal-
      determination switch).
    operands:
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Involves gonad development.
      biological_processes:
      - preferred_term: gonad development
        term:
          id: GO:0008406
          label: gonad development
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Involves sex determination.
      biological_processes:
      - preferred_term: sex determination
        term:
          id: GO:0007530
          label: sex determination
members:
- member: 46,XY complete gonadal dysgenesis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Failure of testis determination in a 46,XY individual (e.g., SRY variants /
      Swyer syndrome): streak gonads, female external genitalia, and Mullerian
      structures despite a Y chromosome.
    gene:
      preferred_term: SRY
      term:
        id: hgnc:11311
        label: SRY
- member: 46,XX testicular disorder of sex development
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Ectopic testis determination in a 46,XX individual, usually from
      translocation of SRY onto an X chromosome — the mirror image of 46,XY
      gonadal dysgenesis, with a male phenotype in a 46,XX karyotype.
    gene:
      preferred_term: SRY
      term:
        id: hgnc:11311
        label: SRY
- member: 46,XX Gonadal Dysgenesis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Failure of ovarian development in a 46,XX individual (e.g., FSHR defects),
      producing streak gonads and hypergonadotropic hypogonadism — the
      female-determination failure of the group.
    gene:
      preferred_term: FSHR
      term:
        id: hgnc:3969
        label: FSHR
notes: >-
  Created by narrowing the over-broad Disorders of Sex Development grouping. The
  differentiating axis is karyotype and the direction of the determination defect
  (testis failure, ovary failure, or ectopic testis). Disorders of androgen
  synthesis/action (HSD17B3, SRD5A2) act downstream of a determined gonad and are
  grouped separately.