# Síndrome distonia-plus

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

## Identificadores

- **ORPHA**: 98203 — https://www.orpha.net/en/disease/detail/98203
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Distonia combinada com outro distúrbio do movimento (por exemplo, mioclonia, parkinsonismo).

## Epidemiologia e herança


## Sinais e sintomas (181 fenótipos HPO)

- **Movimentos hipercinesia** — HPO: HP:0002487
- **Concentração diminuída de ácido homovanílico no LCR** — HPO: HP:0003785
- **Distonia do braço** — HPO: HP:0031960
- **Traço obsessivo-compulsivo** — HPO: HP:0008770
- **Aumento da serotonina sérica** — HPO: HP:0003144
- **Distonia da perna** — HPO: HP:0031959
- **Distonia axial** — HPO: HP:0002530
- **Anormalidade da fala ou vocalização** — HPO: HP:0002167
- **Dispneia** — HPO: HP:0002094
- **Espasticidade do membro inferior** — HPO: HP:0002061
- **Olhar fixo** — HPO: HP:0025401
- **Anormalidade do movimento ocular** — HPO: HP:0000496
- **Atetose** — HPO: HP:0002305
- **Choro inapropriado** — HPO: HP:0030215
- **Anormalidade da coordenação** — HPO: HP:0011443
- **Estridor** — HPO: HP:0010307
- **Rigidez articular** — HPO: HP:0001387
- **Trismo** — HPO: HP:0000211
- **Dificuldade específica de aprendizagem** — HPO: HP:0001328
- **Microcefalia secundária** — HPO: HP:0005484
- **Anormalidade da vasculatura** — HPO: HP:0002597
- **Morfologia anormal do pé** — HPO: HP:0001760
- **Tetraparesia espástica** — HPO: HP:0001285
- **Fraqueza muscular generalizada** — HPO: HP:0003324
- **Reflexos tendinosos profundos hiperativos** — HPO: HP:0006801
- **Crise não motora (ausência) generalizada** — HPO: HP:0002121
- **Alcoolismo** — HPO: HP:0030955
- **Agorafobia** — HPO: HP:0000756
- **Paralisia cerebral** — HPO: HP:0100021
- **Distonia craniofacial** — HPO: HP:0012179
- **Sonolência** — HPO: HP:0002329
- **Vertigem** — HPO: HP:0002321
- **Palidez** — HPO: HP:0000980
- **Anormalidade do metabolismo do ácido carboxílico** — HPO: HP:0004354
- **Vômitos** — HPO: HP:0002013
- **Movimentos anormais da cabeça** — HPO: HP:0002457
- **Apatia** — HPO: HP:0000741
- **Hipotonia generalizada** — HPO: HP:0001290
- **Ataxia da marcha** — HPO: HP:0002066
- **Hipertonia de membro** — HPO: HP:0002509
- _...e mais 141 sintomas. Ver https://raras.org/doenca/sindrome-distonia-plus._

## Genes associados (19)

- **SLC18A2** — Synaptic vesicular amine transporter [Disease-causing germline mutation(s) in]
  - Função: Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient establish
- **ATM** — Serine-protein kinase ATM [Candidate gene tested in]
  - Função: Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a
- **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
- **KCNJ10** — ATP-sensitive inward rectifier potassium channel 10 [Candidate gene tested in]
  - Função: May be responsible for potassium buffering action of glial cells in the brain (By similarity). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow in
- **KCNA1** — Potassium voltage-gated channel subfamily A member 1 [Candidate gene tested in]
  - Função: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:19903818,
- **DRD2** — D(2) dopamine receptor [Candidate gene tested in]
  - Função: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEG
- **TOR1A** — Torsin-1A [Candidate gene tested in]
  - Função: Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates. Involved in the regu
- **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
- **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
- **ATP1A3** — Sodium/potassium-transporting ATPase subunit alpha-3 [Disease-causing germline mutation(s) in]
  - Função: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the e
- **PRRT2** — Proline-rich transmembrane protein 2 [Disease-causing germline mutation(s) in]
  - Função: As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system. In hippocampal neurons, in presynaptic terminals, plays an important role in
- **WARS2** — Tryptophan--tRNA ligase, mitochondrial [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of tRNA(Trp)
- **PNKD** — Probable thioesterase PNKD [Disease-causing germline mutation(s) in]
  - Função: Probable thioesterase that may play a role in cellular detoxification processes; it likely acts on a yet-unknown alpha-hydroxythioester substrate (Probable). In vitro, it is able to catalyze the hydro
- **TMEM151A** — Transmembrane protein 151A [Disease-causing germline mutation(s) in]
- **PRKRA** — Interferon-inducible double-stranded RNA-dependent protein kinase activator A [Disease-causing germline mutation(s) in]
  - Função: Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA produc

## Medicamentos em desenvolvimento (1)

- ZONISAMIDE — Fase Phase 3 (Sodium channel alpha subunit blocker)
- Fonte: https://platform.opentargets.org/disease/MONDO_0020065

## Ensaios clínicos ativos (1)

- **NCT06999096** [NOT_YET_RECRUITING]: Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia — https://clinicaltrials.gov/study/NCT06999096

## Doenças relacionadas (por similaridade fenotípica)

- [Distonia-parkinsonismo infantil](https://raras.org/doenca/distonia-parkinsonismo-infantil) — ORPHA:238455 — 79 sintomas em comum
- [Doença do metabolismo das aminas biogênicas](https://raras.org/doenca/doenca-do-metabolismo-das-aminas-biogenicas) — ORPHA:79169 — 76 sintomas em comum
- [Distonia paroxística](https://raras.org/doenca/distonia-paroxistica) — ORPHA:200037 — 68 sintomas em comum
- [NÃO RARA NA EUROPA: Doença de Parkinson](https://raras.org/doenca/nao-rara-na-europa-doenca-de-parkinson) — ORPHA:319705 — 61 sintomas em comum
- [Distonia sensível à dopa](https://raras.org/doenca/distonia-sensivel-a-dopa) — ORPHA:255 — 54 sintomas em comum
- [Doença de Parkinson de início juvenil](https://raras.org/doenca/doenca-de-parkinson-de-inicio-juvenil) — ORPHA:2828 — 53 sintomas em comum
- [Discinesia paroxística](https://raras.org/doenca/discinesia-paroxistica) — ORPHA:1431 — 53 sintomas em comum
- [Doença do metabolismo da fenilalanina](https://raras.org/doenca/doenca-do-metabolismo-da-fenilalanina) — ORPHA:284814 — 52 sintomas em comum
- [Neurodegenerescência associada a PLA2G6](https://raras.org/doenca/neurodegenerescencia-associada-a-pla2g6) — ORPHA:329303 — 50 sintomas em comum
- [Encefalopatia epiléptica de início precoce inespecífica](https://raras.org/doenca/encefalopatia-epileptica-de-inicio-precoce-inespecifica) — ORPHA:442835 — 49 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 — Síndrome distonia-plus. Disponível em: https://raras.org/doenca/sindrome-distonia-plus
**Formato HTML**: https://raras.org/doenca/sindrome-distonia-plus
**Formato RDF/Turtle**: https://raras.org/api/rdf?orpha=98203