# Síndrome Kallmann

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

## Identificadores

- **ORPHA**: 478 — https://www.orpha.net/en/disease/detail/478
- **CID-10**: E23.0
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

O síndrome de Kallmann (KS) é uma doença genética congénita caracterizada pela associação de hipogonadismo hipogonadotrófico (HH) por deficiência da hormona libertadora de gonadotropina (GnRH), e anosmia ou hiposmia (com hipoplasia ou aplasia do bolbo olfactivo).

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, Multigenic/multifactorial, X-linked recessive

## Sinais e sintomas (87 fenótipos HPO)

- **Hiposmia** — HPO: HP:0004409 (Muito frequente (99-80%))
- **Hábito eunucóide** — HPO: HP:0003782
- **Escroto pequeno** — HPO: HP:0000046
- **Assimetria facial** — HPO: HP:0000324
- **Pelos pubianos esparsos** — HPO: HP:0002225
- **Atrofia testicular** — HPO: HP:0000029
- **Insensibilidade da célula de Leydig à gonadotrofina** — HPO: HP:0002929
- **Agenesia do lobo olfatório** — HPO: HP:0001341
- **Resposta reduzida ao teste de estimulação do hormônio liberador de gonadotrofina** — HPO: HP:0020159
- **Infertilidade** — HPO: HP:0000789
- **Agenesia do corpo caloso** — HPO: HP:0001274
- **Coloboma da íris** — HPO: HP:0000612
- **Ectrodactilia** — HPO: HP:0100257
- **Deficiência intelectual** — HPO: HP:0001249
- **Baixa estatura** — HPO: HP:0004322
- **Atresia de coana** — HPO: HP:0000453
- **Hipoplasia do útero** — HPO: HP:0000013
- **Fenda do lábio superior** — HPO: HP:0000204
- **Hipotelorismo** — HPO: HP:0000601
- **Pectus excavatum** — HPO: HP:0000767
- **Hipermobilidade da articulação interfalângica** — HPO: HP:0006094
- **Agenesia renal unilateral** — HPO: HP:0000122
- **Palato ogival** — HPO: HP:0000218
- **Clinodactilia** — HPO: HP:0030084
- **Anomalia de Duane** — HPO: HP:0009921
- **Nariz bífido** — HPO: HP:0011803
- **Fenda labial** — HPO: HP:0410030
- **Glândula pituitária pequena** — HPO: HP:0012506
- **Genu valgum** — HPO: HP:0002857
- **Deficiência auditiva** — HPO: HP:0000365
- **Anormalidade da dentição** — HPO: HP:0000164
- **Diabetes mellitus** — HPO: HP:0000819
- **Azoospermia** — HPO: HP:0000027
- **Concentração diminuída de hormônio folículo-estimulante circulante** — HPO: HP:0030341
- **Ausência de desenvolvimento puberal** — HPO: HP:0008197
- **Hipoplasia do bulbo olfatório** — HPO: HP:0040326
- **Microfalos** — HPO: HP:0030260
- **Estradiol sérico diminuído** — HPO: HP:0008214
- **Aplasia do bulbo olfatório** — HPO: HP:0032466
- **Concentração sérica de testosterona diminuída** — HPO: HP:0040171
- _...e mais 47 sintomas. Ver https://raras.org/doenca/sindrome-kallmann._

## Genes associados (23)

- **CHD7** — ATP-dependent chromatin remodeler CHD7 [Disease-causing germline mutation(s) in]
  - Função: ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Probable transcription regulator. May be involved in the in 45S precursor rR
- **NSMF** — NMDA receptor synaptonuclear signaling and neuronal migration factor [Disease-causing germline mutation(s) in]
  - Função: Couples NMDA-sensitive glutamate receptor signaling to the nucleus and triggers long-lasting changes in the cytoarchitecture of dendrites and spine synapse processes. Part of the cAMP response element
- **KISS1R** — KiSS-1 receptor [Disease-causing germline mutation(s) in]
  - Função: Receptor for kisspeptins (kisspeptin-10, kisspeptin-13, kisspeptin-14 and metastin/kisspeptin-54) (PubMed:11457843, PubMed:11527393, PubMed:15020672, PubMed:15596153). The hypothalamic KISS1/KISS1R si
- **HS6ST1** — Heparan-sulfate 6-O-sulfotransferase 1 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate. Critical for
- **NDNF** — Protein NDNF [Disease-causing germline mutation(s) in]
  - Função: Secretory protein that plays a role in various cellular processes (PubMed:20969804, PubMed:24706764, PubMed:31883645). Acts as a chemorepellent acting on gonadotropin-releasing hormone (GnRH) expressi
- **FGF17** — Fibroblast growth factor 17 [Disease-causing germline mutation(s) in]
  - Função: Plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain. Required for normal brain development
- **FGF8** — Fibroblast growth factor 8 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Required for normal brain, eye, ear and limb development during embryog
- **DUSP6** — Dual specificity protein phosphatase 6 [Disease-causing germline mutation(s) in]
  - Função: Dual specificity protein phosphatase, which mediates dephosphorylation and inactivation of MAP kinases (PubMed:8670865). Has a specificity for the ERK family (PubMed:8670865). Plays an important role
- **DCC** — Netrin receptor DCC [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger s
- **IL17RD** — Interleukin-17 receptor D [Disease-causing germline mutation(s) in]
  - Função: Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation (PubMed:12807873, PubMed:12958313). Regulates the nuclear ERK signaling pathway by spatially blocking nucl
- **HESX1** — Homeobox expressed in ES cells 1 [Disease-causing germline mutation(s) in]
  - Função: Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromi
- **SOX10** — Transcription factor SOX-10 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Transcription factor that plays a central role in developing and mature glia (By similarity). Specifically activates expression of myelin genes, during oligodendrocyte (OL) maturation, such as DUSP15
- **FEZF1** — Fez family zinc finger protein 1 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Transcription repressor. Involved in the axonal projection and proper termination of olfactory sensory neurons (OSN). Plays a role in rostro-caudal patterning of the diencephalon and in prethalamic fo
- **PROKR2** — Prokineticin receptor 2 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Receptor for prokineticin 2. Exclusively coupled to the G(q) subclass of heteromeric G proteins. Activation leads to mobilization of calcium, stimulation of phosphoinositide turnover and activation of
- **ANOS1** — Anosmin-1 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Has a dual branch-promoting and guidance activity, which may play an important role in the patterning of mitral and tufted cell collaterals to the olfactory cortex (By similarity). Chemoattractant for

## Ensaios clínicos ativos (4)

- **NCT04463316** [RECRUITING]: GROWing Up With Rare GENEtic Syndromes — https://clinicaltrials.gov/study/NCT04463316
- **NCT01601171** [RECRUITING]: Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate — https://clinicaltrials.gov/study/NCT01601171
- **NCT05971836** [ACTIVE_NOT_RECRUITING]: The Molecular Basis of Inherited Reproductive Disorders — https://clinicaltrials.gov/study/NCT05971836
- **NCT04733274** [ACTIVE_NOT_RECRUITING]: Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing — https://clinicaltrials.gov/study/NCT04733274
- **NCT00914823** [COMPLETED]: Kisspeptin Administration in the Adult — https://clinicaltrials.gov/study/NCT00914823
- **NCT01438034** [COMPLETED]: Kisspeptin in the Evaluation of Delayed Puberty — https://clinicaltrials.gov/study/NCT01438034
- **NCT00392756** [COMPLETED]: Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS) — https://clinicaltrials.gov/study/NCT00392756
- **NCT00493961** [COMPLETED]: Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism — https://clinicaltrials.gov/study/NCT00493961
- **NCT00494169** [COMPLETED]: Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders — https://clinicaltrials.gov/study/NCT00494169
- **NCT03687606** [UNKNOWN]: Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH) — https://clinicaltrials.gov/study/NCT03687606

## Doenças relacionadas (por similaridade fenotípica)

- [Deficiências combinadas de hormônios hipofisários, formas genéticas](https://raras.org/doenca/deficiencias-combinadas-de-hormonios-hipofisarios-formas-geneticas) — ORPHA:95494 — 29 sintomas em comum
- [Monossomia parcial do cromossomo 3](https://raras.org/doenca/monossomia-parcial-do-cromossomo-3) — ORPHA:261776 — 24 sintomas em comum
- [Duplicação/triplicação parcial do cromossomo 5](https://raras.org/doenca/duplicacaotriplicacao-parcial-do-cromossomo-5) — ORPHA:262211 — 21 sintomas em comum
- [Síndrome CHARGE](https://raras.org/doenca/sindrome-charge) — ORPHA:138 — 21 sintomas em comum
- [NÃO RARA NA EUROPA: Espectro fenotípico de síndrome FG](https://raras.org/doenca/nao-rara-na-europa-espectro-fenotipico-de-sindrome-fg) — ORPHA:323 — 21 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 — 21 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
- [Defeito do tubo neural](https://raras.org/doenca/defeito-do-tubo-neural) — ORPHA:3388 — 20 sintomas em comum
- [Trissomia parcial do cromossomo 16](https://raras.org/doenca/trissomia-parcial-do-cromossomo-16) — ORPHA:262672 — 20 sintomas em comum
- [Disgenesia gonadal parcial 46,XY](https://raras.org/doenca/disgenesia-gonadal-parcial-46xy) — ORPHA:251510 — 20 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 — Síndrome Kallmann. Disponível em: https://raras.org/doenca/sindrome-kallmann
**Formato HTML**: https://raras.org/doenca/sindrome-kallmann
**Formato RDF/Turtle**: https://raras.org/api/rdf?orpha=478