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46,XX Gonadal Dysgenesis

Summary

2026-04-14
OpenAI MONDO:0009299 Model: gpt-5 8 citations

Summary

MONDO:0009299 provides a dedicated disease-level anchor for 46 XX gonadal dysgenesis. The literature consistently treats this as a rare, genetically heterogeneous ovarian developmental failure state in phenotypically female individuals with a normal 46,XX karyotype, with the core phenotype defined by streak or underdeveloped ovaries, absent spontaneous puberty, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism.

Disease-Anchor Decision

  • Anchor chosen: 46 XX gonadal dysgenesis (MONDO:0009299)
  • Why this anchor: the disease has its own MONDO term and multiple primary human papers describe it as a coherent clinical entity rather than only as a phenotype mention inside broader DSD literature.
  • Why not a generic 46,XX DSD bucket: the core disease definition here is ovarian developmental failure with phenotypically female external genitalia, not generic 46,XX sex-development variation such as prenatal androgen excess.
  • Why not lump fully with broader primary ovarian insufficiency: NR5A1 demonstrates overlap with 46,XX primary ovarian insufficiency, but the 46,XX gonadal dysgenesis literature is narrower and emphasizes congenital streak/underdeveloped ovaries, absent spontaneous puberty, and uterine hypoplasia.
  • Why not split into single-gene disorders for this issue: NUP107, PSMC3IP, FSHR, and NR5A1 all support the same disease-level anchor, and the issue explicitly asked for a disease-level dismech entry rather than a single-gene subtype.

Mechanistic Themes

  • Shared proximal theme: disrupted female gonad development.
  • Shared intermediate theme: impaired ovarian hormonal signaling and folliculogenesis.
  • Shared downstream theme: streak or severely underdeveloped ovaries leading to hypoestrogenic hypergonadotropic ovarian failure.

Papers Used for YAML Evidence

Table (click to expand)
PMID Use in YAML Key contribution
23087880 prevalence framing Rare genetically heterogeneous disease framing
26485283 case definition, pathophysiology, phenotypes, genetics Strong disease-definition abstract plus ovarian-development mechanism
21963259 progression, pathophysiology, phenotypes, genetics Streak gonads, estrogenic signaling, follicular-pool mechanism
7553856 pathophysiology, genetics Direct FSHR signaling defect causing ovarian dysgenesis
8855829 pathophysiology, phenotypes Elevated FSH/LH and amenorrhea in mechanistically defined subset
19246354 pathophysiology, genetics Overlap boundary with broader ovarian insufficiency
35142292 treatment Hormone replacement therapy for secondary sexual characteristics and osteoporosis prevention
31809259 PR framing / differential context MRKH misdiagnosis pitfall and estrogen-dependent uterine visualization

Curation Notes

  • Evidence snippets were restricted to exact quoted text from the cached PMID records.
  • The YAML intentionally avoids generic DSD-management statements as primary treatment evidence; management is limited to hormone replacement therapy with direct PMID-backed wording.
  • The YAML intentionally avoids assigning phenotype frequency bands because the available abstracts support association but not robust quantitative frequency.