# Distonia genética rara

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

## Identificadores

- **ORPHA**: 391799 — https://www.orpha.net/en/disease/detail/391799
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Um caso de distúrbio distônico causado por uma modificação hereditária do genoma do indivíduo.

## Epidemiologia e herança


## Sinais e sintomas (421 fenótipos HPO)

- **Déficit de atenção** — HPO: HP:0000736
- **Infertilidade** — HPO: HP:0000789
- **Amenorreia primária** — HPO: HP:0000786
- **Diabetes mellitus tipo 1** — HPO: HP:0100651
- **Azoospermia** — HPO: HP:0000027
- **Mioclonia espinhal** — HPO: HP:0010531
- **Anormalidade da articulação temporomandibular** — HPO: HP:0010754
- **Nível urinário de dopamina diminuído** — HPO: HP:6000751
- **Cabelo esparso** — HPO: HP:0008070
- **Cifoescoliose** — HPO: HP:0002751
- **Tremor vocal** — HPO: HP:0012477
- **Hiperlipidemia** — HPO: HP:0003077
- **Distrofia muscular** — HPO: HP:0003560
- **Sinal piramidal anormal** — HPO: HP:0007256
- **Aumento da concentração de ácido homovanílico no LCR** — HPO: HP:0034201
- **Dislexia** — HPO: HP:0010522
- **Anormalidade da substância negra** — HPO: HP:0045007
- **Acalasia** — HPO: HP:0002571
- **Edema laríngeo** — HPO: HP:0012027
- **Paralisia pseudobulbar** — HPO: HP:0007024
- **Escoliose** — HPO: HP:0002650
- **Atraso do neurodesenvolvimento** — HPO: HP:0012758
- **Hipomielinização do SNC** — HPO: HP:0003429
- **Transtorno do déficit de atenção com hiperatividade** — HPO: HP:0007018
- **Espermatogênese anormal** — HPO: HP:0008669
- **Hiperlordose lombar** — HPO: HP:0002938
- **Hipoplasia dos vasos linfáticos** — HPO: HP:0003759
- **Bruxismo** — HPO: HP:0003763
- **Contratura articular de membro** — HPO: HP:0003121
- **Distonia oromandibular** — HPO: HP:0012048
- **Disfunção somatossensorial** — HPO: HP:0003474
- **Nível urinário elevado de ácido 5-hidroxi-indolacético** — HPO: HP:6000756
- **Distonia generalizada** — HPO: HP:0007325
- **Flutter ocular** — HPO: HP:0031931
- **Microcefalia secundária** — HPO: HP:0005484
- **Morfologia anormal da musculatura** — HPO: HP:0003011
- **Edema periorbital** — HPO: HP:0100539
- **Reflexos tendinosos profundos hiperativos** — HPO: HP:0006801
- **Choro inapropriado** — HPO: HP:0030215
- **Retrocolis** — HPO: HP:0002544
- _...e mais 381 sintomas. Ver https://raras.org/doenca/distonia-genetica-rara._

## Genes associados (47)

- **TMEM151A** — Transmembrane protein 151A [Disease-causing germline mutation(s) in]
- **VPS16** — Vacuolar protein sorting-associated protein 16 homolog [Disease-causing germline mutation(s) in]
  - Função: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative H
- **ACTB** — Actin, cytoplasmic 1 [Disease-causing germline mutation(s) in]
  - Função: Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (
- **NR4A2** — Nuclear receptor subfamily 4 group A member 2 [Disease-causing germline mutation(s) in]
  - Função: Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development (PubMed:15716272, PubMed:17184956). It is cruci
- **EIF2AK2** — Interferon-induced, double-stranded RNA-activated protein kinase [Disease-causing germline mutation(s) in]
  - Função: IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate
- **NUP54** — Nucleoporin p54 [Disease-causing germline mutation(s) in]
  - Função: Component of the nuclear pore complex, a complex required for the trafficking across the nuclear membrane
- **ARX** — Homeobox protein ARX [Candidate gene tested in]
  - Função: Transcription factor (PubMed:22194193, PubMed:31691806). Binds to specific sequence motif 5'-TAATTA-3' in regulatory elements of target genes, such as histone demethylase KDM5C (PubMed:22194193, PubMe
- **THAP1** — THAP domain-containing protein 1 [Disease-causing germline mutation(s) in]
  - Função: DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modu
- **TUBB4A** — Tubulin beta-4A chain [Disease-causing germline mutation(s) in]
  - Função: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the additio
- **VPS11** — Vacuolar protein sorting-associated protein 11 homolog [Disease-causing germline mutation(s) in]
  - Função: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative H
- **CACNA1A** — Voltage-dependent P/Q-type calcium channel subunit alpha-1A [Candidate gene tested in]
  - Função: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormon
- **VAC14** — Protein VAC14 homolog [Disease-causing germline mutation(s) in]
  - Função: Scaffold protein component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes into a star-shaped
- **SHQ1** — Protein SHQ1 homolog [Disease-causing germline mutation(s) in]
  - Função: Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association wi
- **TAF1** — Transcription initiation factor TFIID subunit 1 [Disease-causing germline mutation(s) in]
  - Função: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or
- **DCAF17** — DDB1- and CUL4-associated factor 17 [Disease-causing germline mutation(s) in]
  - Função: May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex

## Medicamentos em desenvolvimento (4)

- ZONISAMIDE — Fase Phase 3 (Sodium channel alpha subunit blocker)
- INCOBOTULINUMTOXINA — Fase Phase 3 (Synaptosomal nerve-associated protein 25 (SNAP-25) inhibitor)
- LEVETIRACETAM — Fase Phase 2 (Voltage-gated N-type calcium channel alpha-1B subunit blocker)
- ABOBOTULINUMTOXINA — Fase Phase 1 (Synaptosomal nerve-associated protein 25 (SNAP-25) inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0044807

## Ensaios clínicos ativos (1)

- **NCT04319796** [UNKNOWN]: European Registry on Rare Neurological Diseases — https://clinicaltrials.gov/study/NCT04319796

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome distonia-plus](https://raras.org/doenca/sindrome-distonia-plus) — ORPHA:98203 — 179 sintomas em comum
- [Distonia primária de torção](https://raras.org/doenca/distonia-primaria-de-torcao) — ORPHA:156159 — 95 sintomas em comum
- [Distonia sensível à dopa](https://raras.org/doenca/distonia-sensivel-a-dopa) — ORPHA:255 — 93 sintomas em comum
- [NÃO RARA NA EUROPA: Doença de Parkinson](https://raras.org/doenca/nao-rara-na-europa-doenca-de-parkinson) — ORPHA:319705 — 91 sintomas em comum
- [Doença do metabolismo das aminas biogênicas](https://raras.org/doenca/doenca-do-metabolismo-das-aminas-biogenicas) — ORPHA:79169 — 90 sintomas em comum
- [Ataxia espástica](https://raras.org/doenca/ataxia-espastica) — ORPHA:316226 — 90 sintomas em comum
- [Doença do metabolismo da fenilalanina](https://raras.org/doenca/doenca-do-metabolismo-da-fenilalanina) — ORPHA:284814 — 83 sintomas em comum
- [Neurodegenerescência associada a PLA2G6](https://raras.org/doenca/neurodegenerescencia-associada-a-pla2g6) — ORPHA:329303 — 79 sintomas em comum
- [Distonia-parkinsonismo infantil](https://raras.org/doenca/distonia-parkinsonismo-infantil) — ORPHA:238455 — 79 sintomas em comum
- [Distonia focal, segmentar ou multifocal](https://raras.org/doenca/distonia-focal-segmentar-ou-multifocal) — ORPHA:1866 — 78 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 — Distonia genética rara. Disponível em: https://raras.org/doenca/distonia-genetica-rara
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