# Disgenesia gonadal 46,XX

> Página oficial: https://raras.org/doenca/disgenesia-gonadal-46xx
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 243 — https://www.orpha.net/en/disease/detail/243
- **CID-10**: Q99.1
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Diferença do desenvolvimento sexual/anomalia rara no desenvolvimento sexual caracterizada por um defeito ovárico primário, através de uma falha no desenvolvimento das gónadas ou resistência à estimulação de gonadotrofinas que leva à falência ovariana prematura (FOP) em indivíduos 46,XX fenotipicamente femininos.

## Epidemiologia e herança

- **Prevalência**: Unknown
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, Not applicable, X-linked recessive

## Sinais e sintomas (63 fenótipos HPO)

- **Diminuição da circulação do hormônio antimülleriano circulante** — HPO: HP:0031103
- **Morfologia anormal do sistema cardiovascular** — HPO: HP:0030680
- **Morfologia anormal do pênis** — HPO: HP:0000036
- **Atraso de crescimento** — HPO: HP:0001510
- **Má rotação do intestino delgado** — HPO: HP:0004794
- **Estenose pulmonar** — HPO: HP:0001642
- **Anormalidade das glândulas adrenais** — HPO: HP:0000834
- **Fenda orofacial** — HPO: HP:0000202
- **Ausência de desenvolvimento puberal** — HPO: HP:0008197
- **Infertilidade feminina** — HPO: HP:0008222
- **Hipoplasia do ovário** — HPO: HP:0008724
- **Hábito eunucóide** — HPO: HP:0003782
- **Grandes lábios hipoplásicos** — HPO: HP:0000059
- **Estenose da artéria pulmonar** — HPO: HP:0004415
- **Hipoplasia da bexiga** — HPO: HP:0005343
- **Retardo do crescimento intrauterino** — HPO: HP:0001511
- **Oligodramnia** — HPO: HP:0001562
- **Agenesia pulmonar bilateral** — HPO: HP:0005944
- **Defeito do septo ventricular** — HPO: HP:0001629
- **Reversão sexual** — HPO: HP:0012245
- **Orelhas de implantação baixa** — HPO: HP:0000369
- **Hipoplasia pulmonar** — HPO: HP:0002089
- **Hipospadia** — HPO: HP:0000047
- **Aplasia do ovário** — HPO: HP:0010463
- **Agenesia renal** — HPO: HP:0000104
- **Anormalidade dos pelos sexuais secundários** — HPO: HP:0009888 (Muito frequente (99-80%))
- **Maturação esquelética atrasada** — HPO: HP:0002750 (Frequente (79-30%))
- **Amenorreia primária** — HPO: HP:0000786 (Muito frequente (99-80%))
- **Baixa estatura** — HPO: HP:0004322 (Ocasional (29-5%))
- **Aplasia/Hipoplasia do útero** — HPO: HP:0008684 (Frequente (79-30%))
- **Osteoporose das vértebras** — HPO: HP:0005625 (Frequente (79-30%))
- **Densidade mineral óssea reduzida** — HPO: HP:0004349 (Frequente (79-30%))
- **Aracnodactilia** — HPO: HP:0001166 (Raro (<5%))
- **Microcefalia** — HPO: HP:0000252 (Raro (<5%))
- **Estradiol sérico diminuído** — HPO: HP:0008214 (Muito frequente (99-80%))
- **Fertilidade diminuída** — HPO: HP:0000144 (Muito frequente (99-80%))
- **Disgenesia gonadal** — HPO: HP:0000133
- **Anormalidade do metabolismo/homeostase** — HPO: HP:0001939 (Ocasional (29-5%))
- **Aumento do nível circulante de gonadotropina** — HPO: HP:0000837 (Muito frequente (99-80%))
- **Deficiência auditiva** — HPO: HP:0000365 (Ocasional (29-5%))
- _...e mais 23 sintomas. Ver https://raras.org/doenca/disgenesia-gonadal-46xx._

## Genes associados (16)

- **MRPS22** — Small ribosomal subunit protein mS22 [Disease-causing germline mutation(s) in]
- **ESR2** — Estrogen receptor beta [Disease-causing germline mutation(s) in]
  - Função: Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-depen
- **SOHLH1** — Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 [Disease-causing germline mutation(s) in]
  - Função: Transcription regulator of both male and female germline differentiation. Suppresses genes involved in spermatogonial stem cells maintenance, and induces genes important for spermatogonial differentia
- **WNT4** — Protein Wnt-4 [Disease-causing germline mutation(s) in]
  - Função: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Plays an important role in the embryonic development of the urogenital tract and the lung (PubMed:15317892, PubMe
- **HROB** — Homologous recombination OB-fold protein [Disease-causing germline mutation(s) in]
  - Função: DNA-binding protein involved in homologous recombination that acts by recruiting the MCM8-MCM9 helicase complex to sites of DNA damage to promote DNA repair synthesis (PubMed:31467087). A C-terminal r
- **POLR3H** — DNA-directed RNA polymerase III subunit RPC8 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:20413673, PubMed:33558764, PubMed:34675218). Specific periphe
- **FSHR** — Follicle-stimulating hormone receptor [Disease-causing germline mutation(s) (loss of function) in]
  - Função: G protein-coupled receptor for follitropin, the follicle-stimulating hormone (PubMed:11847099, PubMed:24058690, PubMed:24692546). Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK
- **NUP107** — Nuclear pore complex protein Nup107 [Disease-causing germline mutation(s) in]
  - Função: Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:12552102, PubMed:15229283, PubMed:30179222). Required for the assembly of peripheral proteins into the NPC (PubMed:12
- **NR5A1** — Steroidogenic factor 1 [Disease-causing germline mutation(s) in]
  - Função: Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues (PubMed:27378692). Binds to the Ad4 site found in the promoter region of steroidogeni
- **SPIDR** — DNA repair-scaffolding protein [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Plays a role in DNA double-strand break (DBS) repair via homologous recombination (HR). Serves as a scaffolding protein that helps to promote the recruitment of DNA-processing enzymes like the helicas
- **MSH4** — MutS protein homolog 4 [Disease-causing germline mutation(s) in]
  - Função: Involved in meiotic recombination. Required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis
- **ZSWIM7** — Zinc finger SWIM domain-containing protein 7 [Disease-causing germline mutation(s) in]
  - Função: Involved in early stages of the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Required for meiotic progr
- **PSMC3IP** — Homologous-pairing protein 2 homolog [Disease-causing germline mutation(s) in]
  - Função: Plays an important role in meiotic recombination. Stimulates DMC1-mediated strand exchange required for pairing homologous chromosomes during meiosis. The complex PSMC3IP/MND1 binds DNA, stimulates th
- **BMP15** — Bone morphogenetic protein 15 [Disease-causing germline mutation(s) in]
  - Função: May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth
- **BNC1** — Zinc finger protein basonuclin-1 [Disease-causing germline mutation(s) in]
  - Função: Transcriptional activator (By similarity). It is likely involved in the regulation of keratinocytes terminal differentiation in squamous epithelia and hair follicles (PubMed:8034748). Required for the

## Ensaios clínicos ativos (5)

- **NCT07490964** [NOT_YET_RECRUITING]: Polycystic Ovary Syndrome in Type 1 Diabetes — https://clinicaltrials.gov/study/NCT07490964
- **NCT03864068** [COMPLETED]: Inositol Supplementation to Treat PCOS (INSUPP-PCOS) — https://clinicaltrials.gov/study/NCT03864068
- **NCT07298564** [RECRUITING]: Effect of Magnesium and Levocarnitine on Metabolic and Clinical Outcomes in Women With Polycystic Ovarian Syndrome (PCOS) — https://clinicaltrials.gov/study/NCT07298564
- **NCT05555680** [TERMINATED]: Effect of Hyperandrogenism on IVF Outcomes in PCOS Patients — https://clinicaltrials.gov/study/NCT05555680
- **NCT07253454** [NOT_YET_RECRUITING]: Combined Use of Machine Learning and Metabolomics to Improve the Diagnosis and Management of Hyperandrogenism — https://clinicaltrials.gov/study/NCT07253454

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome SERKAL](https://raras.org/doenca/sindrome-serkal) — ORPHA:139466 — 24 sintomas em comum
- [Monossomia parcial do cromossomo 3](https://raras.org/doenca/monossomia-parcial-do-cromossomo-3) — ORPHA:261776 — 23 sintomas em comum
- [Disgenesia gonadal parcial 46,XY](https://raras.org/doenca/disgenesia-gonadal-parcial-46xy) — ORPHA:251510 — 21 sintomas em comum
- [Disgenesia gonadal completa 46,XY](https://raras.org/doenca/disgenesia-gonadal-completa-46xy) — ORPHA:242 — 19 sintomas em comum
- [Síndrome Kallmann](https://raras.org/doenca/sindrome-kallmann) — ORPHA:478 — 19 sintomas em comum
- [Monossomia parcial do cromossomo 4](https://raras.org/doenca/monossomia-parcial-do-cromossomo-4) — ORPHA:261781 — 18 sintomas em comum
- [Monossomia parcial do braço curto do cromossomo 4](https://raras.org/doenca/monossomia-parcial-do-braco-curto-do-cromossomo-4) — ORPHA:261884 — 17 sintomas em comum
- [Síndrome Perrault](https://raras.org/doenca/sindrome-perrault) — ORPHA:2855 — 17 sintomas em comum
- [Síndrome Wolf-Hirschhorn](https://raras.org/doenca/sindrome-wolf-hirschhorn) — ORPHA:280 — 17 sintomas em comum
- [Síndrome Seckel](https://raras.org/doenca/sindrome-seckel) — ORPHA:808 — 16 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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