# Holoprosencefalia

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

## Identificadores

- **ORPHA**: 2162 — https://www.orpha.net/en/disease/detail/2162
- **CID-10**: Q04.2
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A holoprosencefalia (HPE) é uma malformação cerebral complexa resultante da clivagem incompleta do prosencéfalo, entre os dias 18 e 28 de gestação, e que afeta o cérebro anterior e a face, resultando em anomalias neurológicas e faciais de gravidade variável.

## Epidemiologia e herança

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

## Sinais e sintomas (320 fenótipos HPO)

- **Aplasia/Hipoplasia envolvendo o nariz** — HPO: HP:0009924 (Ocasional (29-5%))
- **Agenesia de incisivo** — HPO: HP:0006485
- **Palato duro curto** — HPO: HP:0010290
- **Testa proeminente** — HPO: HP:0011220
- **Orelhas com rotação posterior** — HPO: HP:0000358
- **Corpo caloso fino** — HPO: HP:0033725
- **Ausência de ponto lacrimal** — HPO: HP:0001092
- **Trago subdesenvolvido** — HPO: HP:0011272
- **Assimetria ventricular lateral** — HPO: HP:0100960
- **Anti-hélice proeminente** — HPO: HP:0000395
- **Vermelhão do lábio inferior espesso** — HPO: HP:0000179
- **Cantos da boca voltados para baixo** — HPO: HP:0002714
- **Deficiência intelectual, grave** — HPO: HP:0010864
- **Polidactilia pós-axial da mão** — HPO: HP:0001162
- **Hipoplasia da hipófise anterior** — HPO: HP:0010627
- **Assimetria facial** — HPO: HP:0000324
- **Hipoplasia da maxila** — HPO: HP:0000327
- **Giração cortical anormal** — HPO: HP:0002536
- **Hipotireoidismo** — HPO: HP:0000821
- **Agenesia renal** — HPO: HP:0000104
- **Morfologia anormal do sistema cardiovascular** — HPO: HP:0030680
- **Hemangioma** — HPO: HP:0001028
- **Genitália ambígua** — HPO: HP:0000062
- **Dorso nasal estreito** — HPO: HP:0000446
- **Nascimento prematuro** — HPO: HP:0001622
- **Morfologia anormal da íris** — HPO: HP:0000525
- **Hipossegmentação de núcleos de neutrófilos** — HPO: HP:0011447
- **Atraso global grave do desenvolvimento** — HPO: HP:0011344
- **Hipotonia neonatal** — HPO: HP:0001319
- **Hipogonadismo hipergonadotrófico** — HPO: HP:0000815
- **Estrabismo** — HPO: HP:0000486
- **Anormalidade do sistema genital** — HPO: HP:0000078
- **Asas nasais subdesenvolvidas** — HPO: HP:0000430
- **Anormalidade morfológica do sistema nervoso central** — HPO: HP:0002011
- **Anormalidade da face** — HPO: HP:0000271
- **Vômitos** — HPO: HP:0002013
- **Anormalidade do olho** — HPO: HP:0000478
- **Anormalidade morfológica do trato gastrointestinal** — HPO: HP:0012718
- **Anormalidade do sistema geniturinário** — HPO: HP:0000119
- **Aplasia da foice do cérebro** — HPO: HP:0010654
- _...e mais 280 sintomas. Ver https://raras.org/doenca/holoprosencefalia._

## Genes associados (20)

- **DISP1** — Protein dispatched homolog 1 [Disease-causing germline mutation(s) in]
  - Função: Functions in hedgehog (Hh) signaling. Regulates the release and extracellular accumulation of cholesterol-modified hedgehog proteins and is hence required for effective production of the Hh signal (By
- **SUFU** — Suppressor of fused homolog [Candidate gene tested in]
  - Função: Negative regulator in the hedgehog/smoothened signaling pathway (PubMed:10559945, PubMed:10564661, PubMed:10806483, PubMed:12068298, PubMed:12975309, PubMed:15367681, PubMed:22365972, PubMed:24217340,
- **FGFR1** — Fibroblast growth factor receptor 1 [Candidate gene tested in]
  - Função: Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation a
- **STIL** — SCL-interrupting locus protein [Candidate gene tested in]
  - Função: Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as wel
- **CRIPTO** — Protein Cripto [Candidate gene tested in]
  - Função: GPI-anchored cell membrane protein involved in Nodal signaling. Cell-associated CRIPTO acts as a Nodal coreceptor in cis. Shedding of CRIPTO by TMEM8A modulates Nodal signaling by allowing soluble CRI
- **FOXH1** — Forkhead box protein H1 [Candidate gene tested in]
  - Função: Transcriptional activator. Recognizes and binds to the DNA sequence 5'-TGT[GT][GT]ATT-3'. Required for induction of the goosecoid (GSC) promoter by TGF-beta or activin signaling. Forms a transcription
- **GAS1** — Growth arrest-specific protein 1 [Candidate gene tested in]
  - Função: Specific growth arrest protein involved in growth suppression. Blocks entry to S phase. Prevents cycling of normal and transformed cells. Binds 20(S)-hydroxycholesterol (20(S)-OHC) (By similarity)
- **NODAL** — Nodal homolog [Candidate gene tested in]
  - Função: Essential for mesoderm formation and axial patterning during embryonic development
- **FGF8** — Fibroblast growth factor 8 [Candidate gene tested 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
- **DLL1** — Delta-like protein 1 [Candidate gene tested in]
  - Função: Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner (PubMed:11006133). Following transinte
- **STAG2** — Cohesin subunit SA-2 [Disease-causing germline mutation(s) in]
  - Função: Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chroma
- **GLI2** — Zinc finger protein GLI2 [Disease-causing germline mutation(s) in]
  - Função: Functions as a transcription regulator in the hedgehog (Hh) pathway (PubMed:18455992, PubMed:26565916). Functions as a transcriptional activator (PubMed:19878745, PubMed:24311597, PubMed:9557682). May
- **PTCH1** — Protein patched homolog 1 [Disease-causing germline mutation(s) in]
  - Função: Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a
- **CNOT1** — CCR4-NOT transcription complex subunit 1 [Disease-causing germline mutation(s) in]
  - Função: Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repressio
- **SHH** — Sonic hedgehog protein [Disease-causing germline mutation(s) in]
  - Função: The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-lengt

## Ensaios clínicos ativos (4)

- **NCT00645645** [COMPLETED]: A Study of the Genetic Analysis of Brain Disorders — https://clinicaltrials.gov/study/NCT00645645
- **NCT04691414** [COMPLETED]: Retrospective Study Using Next Generation Sequencing (NGS) on Biological Samples to Improve Genetic Counseling for Patients With Previously Explored Craniofacial Midline Defects. — https://clinicaltrials.gov/study/NCT04691414
- **NCT00088426** [COMPLETED]: Clinical and Genetic Studies on Holoprosencephaly — https://clinicaltrials.gov/study/NCT00088426
- **NCT00005016** [COMPLETED]: Study of the Experiences and Needs of Parents Continuing a Pregnancy Following a Prenatal Diagnosis of Holopresencephaly — https://clinicaltrials.gov/study/NCT00005016

## Doenças relacionadas (por similaridade fenotípica)

- [Holoprosencefalia alobar](https://raras.org/doenca/holoprosencefalia-alobar) — ORPHA:93925 — 141 sintomas em comum
- [Holoprosencefalia lobar](https://raras.org/doenca/holoprosencefalia-lobar) — ORPHA:93924 — 141 sintomas em comum
- [Holoprosencefalia microforma](https://raras.org/doenca/holoprosencefalia-microforma) — ORPHA:280200 — 111 sintomas em comum
- [Monossomia parcial do braço longo do cromossomo 1](https://raras.org/doenca/monossomia-parcial-do-braco-longo-do-cromossomo-1) — ORPHA:262001 — 94 sintomas em comum
- [Síndrome de blefarofimose-perturbação do desenvolvimento intelectual](https://raras.org/doenca/sindrome-de-blefarofimose-perturbacao-do-desenvolvimento-intelectual) — ORPHA:293642 — 81 sintomas em comum
- [Síndrome de hipotonia-transtorno da linguagem-transtorno do desenvolvimento intelectual grave](https://raras.org/doenca/sindrome-de-hipotonia-transtorno-da-linguagem-transtorno-do-desenvolvimento-intelectual-grave) — ORPHA:371364 — 80 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 — 77 sintomas em comum
- [Síndrome 3C](https://raras.org/doenca/sindrome-3c) — ORPHA:7 — 77 sintomas em comum
- [Monossomia parcial do cromossomo 19](https://raras.org/doenca/monossomia-parcial-do-cromossomo-19) — ORPHA:261841 — 74 sintomas em comum
- [Monossomia parcial do cromossomo 3](https://raras.org/doenca/monossomia-parcial-do-cromossomo-3) — ORPHA:261776 — 73 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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**Citação sugerida**: Raras.org — Holoprosencefalia. Disponível em: https://raras.org/doenca/holoprosencefalia
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