# Disgenesia gonadal completa 46,XY > Página oficial: https://raras.org/doenca/disgenesia-gonadal-completa-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**: 242 — https://www.orpha.net/en/disease/detail/242 - **CID-10**: Q99.1 - **OMIM**: none — https://omim.org/entry/none ## Descrição clínica Doença/anomalia rara do desenvolvimento sexual (DDS) associada à ausência no desenvolvimento gonadal que resulta na presença de genitália externa e interna de aparência feminina na presença de um cariótipo 46,XY. ## Epidemiologia e herança - **Prevalência**: Unknown - **Padrão de herança**: Autosomal dominant, Autosomal recessive, X-linked recessive, Y-linked ## Sinais e sintomas (100 fenótipos HPO) - **Disgenesia gonadal com aparência feminina, masculina** — HPO: HP:0008723 - **Hipoplasia do pênis** — HPO: HP:0008736 - **Aplasia/Hipoplasia dos testículos** — HPO: HP:0010468 - **Anormalidade da genitália interna masculina** — HPO: HP:0000022 - **Morfologia anormal da genitália interna feminina** — HPO: HP:0000008 - **Anormalidade da face** — HPO: HP:0000271 - **Testículo ausente** — HPO: HP:0010469 - **Fertilidade diminuída** — HPO: HP:0000144 - **Pé cavo** — HPO: HP:0001761 - **Reflexos tendíneos reduzidos** — HPO: HP:0001315 - **Anormalidade da vagina** — HPO: HP:0000142 - **Fraqueza muscular distal** — HPO: HP:0002460 - **Estradiol sérico diminuído** — HPO: HP:0008214 - **Mielinização periférica anormal** — HPO: HP:0003130 - **Neuropatia atáxica sensorial** — HPO: HP:0003434 - **Comprometimento sensorial distal de todas as modalidades** — HPO: HP:0003409 - **Atrofia do músculo esquelético** — HPO: HP:0003202 - **Anormalidade da condução nervosa periférica** — HPO: HP:0003134 - **Marcha escarvante** — HPO: HP:0003376 - **Infertilidade** — HPO: HP:0000789 - **Hipogonadismo masculino** — HPO: HP:0000026 - **Criptorquidia** — HPO: HP:0000028 - **Anormalidade dos nervos periféricos** — HPO: HP:0045010 - **Neuropatia sensorimotora** — HPO: HP:0007141 - **Aumento do nível circulante de gonadotropina** — HPO: HP:0000837 - **Rugosidade exagerada dos grandes lábios** — HPO: HP:0030913 - **Hipospadia penoscrotal** — HPO: HP:0000808 - **Ovoteste** — HPO: HP:0012861 - **Micropênis** — HPO: HP:0000054 - **Hipospadia perineal** — HPO: HP:0000051 - **Hipoplasia da tuba uterina** — HPO: HP:0008697 - **Disgenesia gonadal, masculina** — HPO: HP:0008668 - **Ovário em fita** — HPO: HP:0010464 - **Anormalidade do epidídimo** — HPO: HP:0009714 - **Testículos displásicos** — HPO: HP:0008733 (Muito frequente (99-80%)) - **Tamanho testicular diminuído** — HPO: HP:0008734 - **Escroto bífido** — HPO: HP:0000048 - **Escroto pequeno** — HPO: HP:0000046 - **Diminuição da circulação do hormônio antimülleriano circulante** — HPO: HP:0031103 - **Ausência de desenvolvimento puberal** — HPO: HP:0008197 - _...e mais 60 sintomas. Ver https://raras.org/doenca/disgenesia-gonadal-completa-46xy._ ## Genes associados (13) - **DHH** — Desert hedgehog protein [Disease-causing germline mutation(s) in] - Função: The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-leng - **AKR1C4** — Aldo-keto reductase family 1 member C4 [Candidate gene tested in] - Função: Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids. Displays broad substrate specificity with distinct positional and stereochemistry, primarily - **AKR1C2** — Aldo-keto reductase family 1 member C2 [Disease-causing germline mutation(s) in] - Função: Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids. Displays broad substrate specificity with distinct positional and stereochemistry, primarily - **ZFPM2** — Zinc finger protein ZFPM2 [Disease-causing germline mutation(s) in] - Função: Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis. Essential cof - **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 - **MAP3K1** — Mitogen-activated protein kinase kinase kinase 1 [Disease-causing germline mutation(s) in] - Função: Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MA - **DHX37** — Probable ATP-dependent RNA helicase DHX37 [Disease-causing germline mutation(s) 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 - **CBX2** — Chromobox protein homolog 2 [Disease-causing germline mutation(s) (loss of function) in] - Função: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout developme - **WT1** — Wilms tumor protein [Candidate gene tested in] - Função: Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:17716689, PubMed:2525 - **DMRT1** — Doublesex- and mab-3-related transcription factor 1 [Role in the phenotype of] - Função: Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation. Plays a central role in spermatogonia by in - **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 - **SRY** — Sex-determining region Y protein [Disease-causing germline mutation(s) (loss of function) 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 - **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 ## Ensaios clínicos ativos (1) - **NCT04708431** [RECRUITING]: Androgen Receptor, Implications for Health and Wellbeing: Natural History Study of Individuals With Androgen Insensitivity — https://clinicaltrials.gov/study/NCT04708431 ## Doenças relacionadas (por similaridade fenotípica) - [Disgenesia gonadal parcial 46,XY](https://raras.org/doenca/disgenesia-gonadal-parcial-46xy) — ORPHA:251510 — 59 sintomas em comum - [Síndrome de disgenesia gonadal 46,XY-neuropatia sensitiva e motora](https://raras.org/doenca/sindrome-de-disgenesia-gonadal-46xy-neuropatia-sensitiva-e-motora) — ORPHA:168563 — 32 sintomas em comum - [Doença do desenvolvimento sexual 46,XX](https://raras.org/doenca/doenca-do-desenvolvimento-sexual-46xx) — ORPHA:2982 — 28 sintomas em comum - [Monossomia parcial do cromossomo 3](https://raras.org/doenca/monossomia-parcial-do-cromossomo-3) — ORPHA:261776 — 26 sintomas em comum - [Síndrome de regressão testicular](https://raras.org/doenca/sindrome-de-regressao-testicular) — ORPHA:983 — 22 sintomas em comum - [Trissomia parcial do cromossomo 16](https://raras.org/doenca/trissomia-parcial-do-cromossomo-16) — ORPHA:262672 — 20 sintomas em comum - [Trissomia parcial do braço curto do cromossomo 16](https://raras.org/doenca/trissomia-parcial-do-braco-curto-do-cromossomo-16) — ORPHA:262794 — 20 sintomas em comum - [Doença do desenvolvimento sexual 46,XX testicular](https://raras.org/doenca/doenca-do-desenvolvimento-sexual-46xx-testicular) — ORPHA:393 — 20 sintomas em comum - [Disgenesia gonadal 46,XX](https://raras.org/doenca/disgenesia-gonadal-46xx) — ORPHA:243 — 19 sintomas em comum - [Síndrome Smith-Lemli-Opitz](https://raras.org/doenca/sindrome-smith-lemli-opitz) — ORPHA:818 — 19 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. --- **Citação sugerida**: Raras.org — Disgenesia gonadal completa 46,XY. Disponível em: https://raras.org/doenca/disgenesia-gonadal-completa-46xy **Formato HTML**: https://raras.org/doenca/disgenesia-gonadal-completa-46xy **Formato RDF/Turtle**: https://raras.org/api/rdf?orpha=242