# Doença do desenvolvimento sexual 46,XY

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

## Identificadores

- **ORPHA**: 98085 — https://www.orpha.net/en/disease/detail/98085
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Diferenças do Desenvolvimento Sexual em pessoas com o conjunto de cromossomos 46,XY.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000

## Sinais e sintomas (495 fenótipos HPO)

- **Polegar largo** — HPO: HP:0011304
- **Hemorragia retal** — HPO: HP:6001316
- **Testículo ausente** — HPO: HP:0010469
- **Fístula uretrovaginal** — HPO: HP:0008716
- **Genitália externa ausente** — HPO: HP:0000042
- **Hemoglobina anormal** — HPO: HP:0011902
- **Comportamento atípico** — HPO: HP:0000708
- **Anemia** — HPO: HP:0001903
- **Contratura em flexão** — HPO: HP:0001371
- **Oftalmoplegia** — HPO: HP:0000602
- **Fisiologia anormal do sistema nervoso autônomo** — HPO: HP:0012332
- **Apneia do sono** — HPO: HP:0010535
- **Autismo** — HPO: HP:0000717
- **Comportamento autolesivo** — HPO: HP:0100716
- **Anormalidade do movimento** — HPO: HP:0100022
- **Anormalidade do colo do útero** — HPO: HP:0012888
- **Alta estatura** — HPO: HP:0000098
- **Nível anormal de hormônio folículo-estimulante circulante** — HPO: HP:0030346
- **Acne** — HPO: HP:0001061
- **Morfologia anormal do ducto deferente** — HPO: HP:0012872
- **Cegueira** — HPO: HP:0000618
- **Miopia** — HPO: HP:0000545
- **Infecções do trato urinário recorrentes** — HPO: HP:0000010
- **Mioclonias** — HPO: HP:0001336
- **Aplasia/Hipoplasia da tuba uterina** — HPO: HP:0008655
- **Pelos pubianos ausentes** — HPO: HP:0002555
- **Vermelhão do lábio superior em tenda** — HPO: HP:0010804
- **Anormalidade do sono** — HPO: HP:0002360
- **Sialorreia** — HPO: HP:0002307
- **Atraso motor** — HPO: HP:0001270
- **Atraso global profundo do desenvolvimento** — HPO: HP:0012736
- **Face plana** — HPO: HP:0012368
- **Anormalidade das fontanelas** — HPO: HP:0011328
- **Volvulus** — HPO: HP:0002580
- **Encefalite infecciosa** — HPO: HP:0002383
- **Megacólon agangliônico** — HPO: HP:0002251
- **Atrofia cortical cerebral** — HPO: HP:0002120
- **Morfologia anormal do coração** — HPO: HP:0001627
- **Deslocamento do meato uretral** — HPO: HP:0100627
- **Retorno venoso pulmonar anômalo** — HPO: HP:0010772
- _...e mais 455 sintomas. Ver https://raras.org/doenca/doenca-do-desenvolvimento-sexual-46xy._

## Genes associados (24)

- **SRD5A2** — 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [Disease-causing germline mutation(s) in]
  - Função: Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation an
- **DHX37** — Probable ATP-dependent RNA helicase DHX37 [Candidate gene tested in]
  - Função: ATP-binding RNA helicase that plays a role in maturation of the small ribosomal subunit in ribosome biogenesis (PubMed:30582406). Required for the release of the U3 snoRNP from pre-ribosomal particles
- **WWOX** — WW domain-containing oxidoreductase [Candidate gene tested in]
  - Função: Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic
- **VAMP7** — Vesicle-associated membrane protein 7 [Candidate gene tested in]
  - Função: Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome. Required for heterotypic fusion of late end
- **MTM1** — Myotubularin [Candidate gene tested in]
  - Função: Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (PubMed:10900271, PubMed:11001925, PubMed:12646134, PubMed:14
- **SRY** — Sex-determining region Y protein [Candidate gene tested in]
  - Função: Transcriptional regulator that controls a genetic switch in male development (PubMed:11563911). It is necessary and sufficient for initiating male sex determination by directing the development of sup
- **MAMLD1** — Mastermind-like domain-containing protein 1 [Candidate gene tested in]
  - Função: Transactivates the HES3 promoter independently of NOTCH proteins. HES3 is a non-canonical NOTCH target gene which lacks binding sites for RBPJ
- **BDNF** — Neurotrophic factor BDNF precursor form [Candidate gene tested in]
  - Função: Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of
- **PPP2R3C** — Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [Candidate gene tested in]
  - Função: May regulate MCM3AP phosphorylation through phosphatase recruitment (By similarity). May act as a negative regulator of ABCB1 expression and function through the dephosphorylation of ABCB1 by TFPI2/PP
- **PAX6** — Paired box protein Pax-6 [Candidate gene tested in]
  - Função: Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells (By similarity)
- **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
- **NR0B1** — Nuclear receptor subfamily 0 group B member 1 [Disease-causing germline mutation(s) in]
  - Função: Nuclear receptor that lacks a DNA-binding domain and acts as a corepressor that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions (PubMed:12482977, Pu
- **ATRX** — Transcriptional regulator ATRX [Disease-causing germline mutation(s) in]
  - Função: Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Bi
- **SOX9** — Transcription factor SOX-9 [Disease-causing germline mutation(s) in]
  - Função: Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:24038782). Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enha
- **AR** — Androgen receptor [Disease-causing germline mutation(s) in]
  - Função: Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).

## Ensaios clínicos ativos (1)

- **NCT06065852** [RECRUITING]: National Registry of Rare Kidney Diseases — https://clinicaltrials.gov/study/NCT06065852

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome de alfa-talassemia-transtorno do desenvolvimento intelectual ligada ao X](https://raras.org/doenca/sindrome-de-alfa-talassemia-transtorno-do-desenvolvimento-intelectual-ligada-ao-x) — ORPHA:847 — 102 sintomas em comum
- [Monossomia parcial do cromossomo 3](https://raras.org/doenca/monossomia-parcial-do-cromossomo-3) — ORPHA:261776 — 96 sintomas em comum
- [Disgenesia gonadal completa 46,XY](https://raras.org/doenca/disgenesia-gonadal-completa-46xy) — ORPHA:242 — 87 sintomas em comum
- [Síndrome de blefarofimose-perturbação do desenvolvimento intelectual](https://raras.org/doenca/sindrome-de-blefarofimose-perturbacao-do-desenvolvimento-intelectual) — ORPHA:293642 — 87 sintomas em comum
- [Síndrome de Kleefstra](https://raras.org/doenca/sindrome-de-kleefstra) — ORPHA:261494 — 85 sintomas em comum
- [Disgenesia gonadal parcial 46,XY](https://raras.org/doenca/disgenesia-gonadal-parcial-46xy) — ORPHA:251510 — 84 sintomas em comum
- [Monossomia parcial do braço curto do cromossomo 1](https://raras.org/doenca/monossomia-parcial-do-braco-curto-do-cromossomo-1) — ORPHA:261857 — 83 sintomas em comum
- [Síndrome Smith-Lemli-Opitz](https://raras.org/doenca/sindrome-smith-lemli-opitz) — ORPHA:818 — 81 sintomas em comum
- [Síndrome aneuploidia variada em mosaico](https://raras.org/doenca/sindrome-aneuploidia-variada-em-mosaico) — ORPHA:1052 — 80 sintomas em comum
- [Trissomia parcial do cromossomo 16](https://raras.org/doenca/trissomia-parcial-do-cromossomo-16) — ORPHA:262672 — 78 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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