# Holoprosencefalia lobar

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

## Identificadores

- **ORPHA**: 93924 — https://www.orpha.net/en/disease/detail/93924
- **CID-10**: Q04.2
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A holoprosencefalia lobar é a forma clássica mais ligeira de holoprosencefalia (HPE, ver este termo), caracterizada pela separação dos hemisférios cerebrais direito e esquerdo e ventrículos laterais com alguma continuidade em todo o neocórtex frontal, especialmente rostralmente e ventralmente.

## Epidemiologia e herança

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

## Sinais e sintomas (141 fenótipos HPO)

- **Letargia** — HPO: HP:0001254 (Ocasional (29-5%))
- **Criptorquidia** — HPO: HP:0000028
- **Micropênis** — HPO: HP:0000054
- **Nariz curto** — HPO: HP:0003196
- **Epicanto** — HPO: HP:0000286
- **Agenesia de incisivo** — HPO: HP:0006485
- **Ptose** — HPO: HP:0000508
- **Filtro curto** — HPO: HP:0000322
- **Agenesia parcial do corpo caloso** — HPO: HP:0001338
- **Microftalmia** — HPO: HP:0000568
- **Palato duro curto** — HPO: HP:0010290
- **Testa proeminente** — HPO: HP:0011220
- **Hipoplasia da pré-maxila** — HPO: HP:0010650
- **Fenda palatina bilateral** — HPO: HP:0100337
- **Atresia de coana** — HPO: HP:0000453
- **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
- **Pescoço curto** — HPO: HP:0000470
- **Achatamento malar** — HPO: HP:0000272
- **Anti-hélice proeminente** — HPO: HP:0000395
- **Vermelhão do lábio inferior espesso** — HPO: HP:0000179
- **Meningocele occipital** — HPO: HP:0002436
- **Ponta nasal larga** — HPO: HP:0000455
- **Cantos da boca voltados para baixo** — HPO: HP:0002714
- **Deficiência intelectual, grave** — HPO: HP:0010864
- **Anoſtalmia** — HPO: HP:0000528
- **Fenda labial bilateral** — HPO: HP:0100336
- **Retrusão médio-facial** — HPO: HP:0011800
- **Polidactilia pós-axial da mão** — HPO: HP:0001162
- **Hipoplasia da hipófise anterior** — HPO: HP:0010627
- **Apêndice cutâneo pré-auricular** — HPO: HP:0000384
- **Assimetria facial** — HPO: HP:0000324
- **Fenda do lábio superior** — HPO: HP:0000204
- **Hipoplasia da maxila** — HPO: HP:0000327
- **Giração cortical anormal** — HPO: HP:0002536
- **Fontanela anterior ampla** — HPO: HP:0000260
- **Agenesia da hipófise anterior** — HPO: HP:0010626
- _...e mais 101 sintomas. Ver https://raras.org/doenca/holoprosencefalia-lobar._

## Genes associados (16)

- **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
- **NODAL** — Nodal homolog [Disease-causing germline mutation(s) in]
  - Função: Essential for mesoderm formation and axial patterning during embryonic development
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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)
- **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)
- **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
- **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

## Doenças relacionadas (por similaridade fenotípica)

- [Holoprosencefalia alobar](https://raras.org/doenca/holoprosencefalia-alobar) — ORPHA:93925 — 141 sintomas em comum
- [Holoprosencefalia microforma](https://raras.org/doenca/holoprosencefalia-microforma) — ORPHA:280200 — 85 sintomas em comum
- [Holoprosencefalia, variante inter-hemisférica média](https://raras.org/doenca/holoprosencefalia-variante-inter-hemisferica-media) — ORPHA:93926 — 72 sintomas em comum
- [Holoprosencefalia semilobar](https://raras.org/doenca/holoprosencefalia-semilobar) — ORPHA:220386 — 72 sintomas em comum
- [Monossomia parcial do cromossomo 3](https://raras.org/doenca/monossomia-parcial-do-cromossomo-3) — ORPHA:261776 — 46 sintomas em comum
- [Síndrome de blefarofimose-perturbação do desenvolvimento intelectual](https://raras.org/doenca/sindrome-de-blefarofimose-perturbacao-do-desenvolvimento-intelectual) — ORPHA:293642 — 45 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 — 45 sintomas em comum
- [Síndrome White-Sutton](https://raras.org/doenca/sindrome-white-sutton) — ORPHA:468678 — 44 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 — 44 sintomas em comum
- [Monossomia parcial do braço longo do cromossomo 14](https://raras.org/doenca/monossomia-parcial-do-braco-longo-do-cromossomo-14) — ORPHA:262110 — 44 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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