# Holoprosencefalia semilobar

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

## Identificadores

- **ORPHA**: 220386 — https://www.orpha.net/en/disease/detail/220386
- **CID-10**: Q04.2

## Descrição clínica

A holoprosencefalia semilobar é uma das formas clássicas de holoprosencefalia (HPE, ver este termo) em que os lobos frontais e parietais esquerdo e direito estão fundidos e a fissura inter-hemisférica está presente apenas posteriormente.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Multigenic/multifactorial, Not applicable

## Sinais e sintomas (72 fenótipos HPO)

- **Narina única** — HPO: HP:0009932 (Ocasional (29-5%))
- **Anormalidade morfológica do trato gastrointestinal** — HPO: HP:0012718 (Ocasional (29-5%))
- **Variabilidade anormal da frequência cardíaca** — HPO: HP:0031860 (Ocasional (29-5%))
- **Deficiência visual cerebral** — HPO: HP:0100704 (Frequente (79-30%))
- **Distúrbio do ciclo sono-vigília** — HPO: HP:0006979 (Frequente (79-30%))
- **Doença pulmonar crônica** — HPO: HP:0006528 (Frequente (79-30%))
- **Alimentação por gastrostomia na infância** — HPO: HP:0011471 (Ocasional (29-5%))
- **Probóscide** — HPO: HP:0012806 (Ocasional (29-5%))
- **Fisiologia anormal do hipotálamo** — HPO: HP:0012285 (Frequente (79-30%))
- **Baixa estatura** — HPO: HP:0004322 (Muito frequente (99-80%))
- **Hipotonia axial** — HPO: HP:0008936 (Ocasional (29-5%))
- **Apneia central** — HPO: HP:0002871 (Frequente (79-30%))
- **Pneumonia por aspiração** — HPO: HP:0011951 (Frequente (79-30%))
- **Defeito do tubo neural** — HPO: HP:0045005 (Frequente (79-30%))
- **Transtorno do déficit de atenção com hiperatividade** — HPO: HP:0007018 (Frequente (79-30%))
- **Incisivo maxilar mediano único** — HPO: HP:0006315 (Ocasional (29-5%))
- **Anormalidade dos membros** — HPO: HP:0040064 (Ocasional (29-5%))
- **Instabilidade de temperatura** — HPO: HP:0005968 (Frequente (79-30%))
- **Dificuldades alimentares** — HPO: HP:0011968 (Muito frequente (99-80%))
- **Apraxia oromotora** — HPO: HP:0007301 (Frequente (79-30%))
- **Ciclopia** — HPO: HP:0009914 (Ocasional (29-5%))
- **Anormalidade da função motora central** — HPO: HP:0011442 (Frequente (79-30%))
- **Fala ausente** — HPO: HP:0001344 (Frequente (79-30%))
- **Deficiência auditiva neurossensorial** — HPO: HP:0000407 (Frequente (79-30%))
- **Agenesia do corpo caloso** — HPO: HP:0001274 (Ocasional (29-5%))
- **Fissura palatina** — HPO: HP:0000175 (Frequente (79-30%))
- **Deficiência intelectual** — HPO: HP:0001249 (Frequente (79-30%))
- **Distonia de membro** — HPO: HP:0002451 (Frequente (79-30%))
- **Anormalidade do sistema esquelético** — HPO: HP:0000924 (Ocasional (29-5%))
- **Luxação do quadril** — HPO: HP:0002827 (Ocasional (29-5%))
- **Escoliose** — HPO: HP:0002650 (Ocasional (29-5%))
- **Irritabilidade** — HPO: HP:0000737 (Frequente (79-30%))
- **Anormalidade do olho** — HPO: HP:0000478 (Muito frequente (99-80%))
- **Úvula bífida** — HPO: HP:0000193 (Frequente (79-30%))
- **Microcefalia** — HPO: HP:0000252 (Frequente (79-30%))
- **Morfologia anormal do tronco cerebral** — HPO: HP:0002363 (Frequente (79-30%))
- **Constipação** — HPO: HP:0002019 (Frequente (79-30%))
- **Hidrocefalia** — HPO: HP:0000238 (Ocasional (29-5%))
- **Apatia** — HPO: HP:0000741 (Frequente (79-30%))
- **Letargia** — HPO: HP:0001254 (Frequente (79-30%))
- _...e mais 32 sintomas. Ver https://raras.org/doenca/holoprosencefalia-semilobar._

## Genes associados (18)

- **ZIC2** — Zinc finger protein ZIC 2 [Disease-causing germline mutation(s) in]
  - Função: Acts as a transcriptional activator or repressor. Plays important roles in the early stage of organogenesis of the CNS. Activates the transcription of the serotonin transporter SERT in uncrossed ipsil
- **FGF8** — Fibroblast growth factor 8 [Disease-causing germline mutation(s) 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
- **SIX3** — Homeobox protein SIX3 [Disease-causing germline mutation(s) in]
  - Função: Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development re
- **DLL1** — Delta-like protein 1 [Disease-causing germline mutation(s) 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
- **CDON** — Cell adhesion molecule-related/down-regulated by oncogenes [Disease-causing germline mutation(s) in]
  - Função: Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells (By similarity)
- **NODAL** — Nodal homolog [Disease-causing germline mutation(s) in]
  - Função: Essential for mesoderm formation and axial patterning during embryonic development
- **TGIF1** — Homeobox protein TGIF1 [Disease-causing germline mutation(s) in]
  - Função: Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activati
- **GAS1** — Growth arrest-specific protein 1 [Disease-causing germline mutation(s) 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)
- **FOXH1** — Forkhead box protein H1 [Disease-causing germline mutation(s) 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
- **STIL** — SCL-interrupting locus protein [Disease-causing germline mutation(s) 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
- **STAG2** — Cohesin subunit SA-2 [Disease-causing germline mutation(s) (loss of function) 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
- **SMC1A** — Structural maintenance of chromosomes protein 1A [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication.
- **CRIPTO** — Protein Cripto [Disease-causing germline mutation(s) 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
- **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
- **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

## Doenças relacionadas (por similaridade fenotípica)

- [Holoprosencefalia, variante inter-hemisférica média](https://raras.org/doenca/holoprosencefalia-variante-inter-hemisferica-media) — ORPHA:93926 — 72 sintomas em comum
- [Holoprosencefalia alobar](https://raras.org/doenca/holoprosencefalia-alobar) — ORPHA:93925 — 72 sintomas em comum
- [Holoprosencefalia lobar](https://raras.org/doenca/holoprosencefalia-lobar) — ORPHA:93924 — 72 sintomas em comum
- [Síndrome epiléptico de início neonatal-infantil](https://raras.org/doenca/sindrome-epileptico-de-inicio-neonatal-infantil) — ORPHA:693802 — 24 sintomas em comum
- [Síndrome de perturbação do desenvolvimento intelectual DYRK1A-relacionada](https://raras.org/doenca/sindrome-de-perturbacao-do-desenvolvimento-intelectual-dyrk1a-relacionada) — ORPHA:464306 — 24 sintomas em comum
- [Polimicrogiria bilateral](https://raras.org/doenca/polimicrogiria-bilateral) — ORPHA:268940 — 23 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 — 23 sintomas em comum
- [Síndrome de hiperfosfatemia-transtorno do desenvolvimento intelectual](https://raras.org/doenca/sindrome-de-hiperfosfatemia-transtorno-do-desenvolvimento-intelectual) — ORPHA:247262 — 22 sintomas em comum
- [Duplicação/triplicação parcial do cromossomo 5](https://raras.org/doenca/duplicacaotriplicacao-parcial-do-cromossomo-5) — ORPHA:262211 — 22 sintomas em comum
- [Monossomia parcial do braço longo do cromossomo 21](https://raras.org/doenca/monossomia-parcial-do-braco-longo-do-cromossomo-21) — ORPHA:262173 — 22 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 semilobar. Disponível em: https://raras.org/doenca/holoprosencefalia-semilobar
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