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Distonia isolada generalizada
ORPHA:376724PCDT · SUSDOENÇA RARA

Hipercinesia refere-se a um aumento na atividade muscular que pode resultar em movimentos excessivos, sejam anormais, normais ou combinados. A hipercinesia é um estado de inquietação excessiva que é apresentado em uma grande variedade de distúrbios que afetam a capacidade de controlar o movimento motor, como a doença de Huntington. É o oposto da hipocinesia, que se refere à diminuição do movimento corporal, como comumente manifestado na doença de Parkinson.

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Introdução

O que você precisa saber de cara

📋

Distonia isolada generalizada é um distúrbio do movimento caracterizado por contrações musculares involuntárias e sustentadas, afetando múltiplos grupos musculares. Pode apresentar-se com hipotonia, distúrbios da marcha, disartria e outras manifestações neurológicas, associada a mutações em genes como TOR1A e THAP1.

Publicações científicas
6 artigos
Último publicado: 2024 Aug 20
🏥
SUS: Cobertura mínimaScore: 30%
PCDT disponível
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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

💪
Músculos
15 sintomas
🧠
Neurológico
7 sintomas
🦴
Ossos e articulações
3 sintomas
🫃
Digestivo
1 sintomas
🫘
Rins
1 sintomas
😀
Face
1 sintomas

+ 11 sintomas em outras categorias

Características mais comuns

Mioclonias
Distonia generalizada
Morfologia anormal da musculatura
Anormalidade da voz
Blefaroespasmo
Distonia laríngea
39sintomas
Sem dados (39)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 39 características clínicas mais associadas, ordenadas por frequência.

MiocloniasMyoclonus
Distonia generalizadaGeneralized dystonia
Morfologia anormal da musculaturaAbnormality of the musculature
Anormalidade da vozAbnormality of the voice
BlefaroespasmoBlepharospasm

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa2desde 2024
Total histórico6PubMed
Últimos 10 anos6publicações
Pico20202 papers
Linha do tempo
2024Hoje · 2026🧪 2021Primeiro ensaio clínico
Publicações por ano (últimos 10 anos)

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Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

4 genes identificados com associação a esta condição.

TOR1ATorsin-1ADisease-causing germline mutation(s) inTolerante
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 regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specificall

LOCALIZAÇÃO

Endoplasmic reticulum lumenNucleus membraneCell projection, growth coneCytoplasmic vesicle membraneCytoplasmic vesicle, secretory vesicleCytoplasmic vesicle, secretory vesicle, synaptic vesicleCytoplasm, cytoskeleton

VIAS BIOLÓGICAS (1)
Cargo recognition for clathrin-mediated endocytosis
MECANISMO DE DOENÇA

Dystonia 1, torsion, autosomal dominant

A primary torsion dystonia, and the most common and severe form. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 1 is characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body, in the absence of other neurological symptoms. Typically, symptoms develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. 'Torsion' refers to the twisting nature of body movements observed in DYT1, often affecting the trunk. Distribution and severity of symptoms vary widely between affected individuals, ranging from mild focal dystonia to severe generalized dystonia, even within families.

EXPRESSÃO TECIDUAL(Ubíquo)
Fibroblastos
47.1 TPM
Útero
27.4 TPM
Aorta
26.7 TPM
Linfócitos
26.6 TPM
Artéria tibial
25.9 TPM
OUTRAS DOENÇAS (3)
early-onset generalized limb-onset dystoniaarthrogryposis multiplex congenita 5myoclonus-dystonia syndrome
HGNC:3098UniProt:O14656
SHQ1Protein SHQ1 homologCandidate gene tested inTolerante
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 with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA

LOCALIZAÇÃO

Cytoplasm, cytosolNucleus, nucleoplasm

VIAS BIOLÓGICAS (1)
Telomere Extension By Telomerase
MECANISMO DE DOENÇA

Dystonia 35, childhood-onset

A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT35 is an autosomal recessive form characterized by the onset of a dystonic movement disorder in the first year of life.

EXPRESSÃO TECIDUAL(Ubíquo)
Fibroblastos
12.3 TPM
Linfócitos
10.4 TPM
Testículo
9.1 TPM
Cervix Endocervix
8.1 TPM
Tireoide
7.7 TPM
OUTRAS DOENÇAS (3)
neurodevelopmental disorder with dystonia and seizuresdystonia 35, childhood-onsetearly-onset generalized limb-onset dystonia
HGNC:25543UniProt:Q6PI26
THAP1THAP domain-containing protein 1Disease-causing germline mutation(s) inRestrito
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 modulating expression of pRB-E2F cell-cycle target genes, including RRM1. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. May also have pro-apoptotic activity by potentiating both serum-withdrawal and TNF-induced apoptosis

LOCALIZAÇÃO

Nucleus, nucleoplasmNucleus, PML body

MECANISMO DE DOENÇA

Dystonia 6, torsion

A primary torsion dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 6 is characterized by onset in early adulthood, cranial or cervical involvement in about half of the cases, and frequent progression to involve multiple body regions.

EXPRESSÃO TECIDUAL(Ubíquo)
Testículo
14.9 TPM
Fibroblastos
13.7 TPM
Linfócitos
13.5 TPM
Útero
10.9 TPM
Esôfago - Muscular
10.4 TPM
OUTRAS DOENÇAS (1)
torsion dystonia 6
HGNC:20856UniProt:Q9NVV9
EIF2AK2Interferon-induced, double-stranded RNA-activated protein kinaseCandidate gene tested inTolerante
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 immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral in

LOCALIZAÇÃO

CytoplasmNucleusCytoplasm, perinuclear region

VIAS BIOLÓGICAS (6)
ISG15 antiviral mechanismInterferon alpha/beta signalingPKR-mediated signalingInhibition of PKREvasion by RSV of host interferon responses
MECANISMO DE DOENÇA

Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome

An autosomal dominant disorder characterized by global developmental delay apparent in early childhood, cognitive impairment, ataxia, poor or absent speech with dysarthria, hypotonia, hypertonia, extrapyramidal signs, tremor, and abnormal involuntary movements. Affected individuals also exhibit neurological regression in the setting of febrile illness or infection. Many patients have seizures. Brain imaging shows diffuse white matter abnormalities with poor myelination.

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
62.0 TPM
Fibroblastos
24.7 TPM
Útero
21.9 TPM
Cervix Ectocervix
21.1 TPM
Cervix Endocervix
20.4 TPM
OUTRAS DOENÇAS (3)
leukoencephalopathy, developmental delay, and episodic neurologic regression syndromedystonia 33early-onset generalized limb-onset dystonia
HGNC:9437UniProt:P19525

Variantes genéticas (ClinVar)

218 variantes patogênicas registradas no ClinVar.

🧬 EIF2AK2: NM_001135651.3(EIF2AK2):c.655A>C (p.Ser219Arg) ()
🧬 EIF2AK2: NM_001135651.3(EIF2AK2):c.1642C>T (p.Arg548Ter) ()
🧬 EIF2AK2: NM_001135651.3(EIF2AK2):c.1067G>T (p.Arg356Met) ()
🧬 EIF2AK2: NM_001135651.3(EIF2AK2):c.1310C>A (p.Thr437Lys) ()
🧬 EIF2AK2: NM_001135651.3(EIF2AK2):c.535T>A (p.Ser179Thr) ()
Ver todas no ClinVar

Diagnóstico

Os sinais que médicos procuram e os exames que confirmam

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Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Pipeline de tratamentos
Pipeline regulatório — de medicamentos já aprovados a drogas em pesquisa exploratória.
2Fase 21
·Pré-clínico1
Medicamentos catalogadosEnsaios clínicos· 0 medicamentos · 2 ensaios
Carregando informações de tratamento...

Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Distonia isolada generalizada

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Selecione um estado ou use sua localização para ver resultados.

Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.

Pesquisa ativa

Ensaios clínicos abertos e novidades científicas recentes

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1 pesquisa recrutando participantes. Converse com seu médico sobre a possibilidade de participar.

Outros ensaios clínicos

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Distribuição por fase
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Publicações mais relevantes

Timeline de publicações
6 papers (10 anos)
#1

Pallidal Versus Subthalamic Deep-Brain Stimulation for Generalized Isolated Dystonia: A Retrospective Study.

Journal of clinical medicine2024 Aug 20

Objectives: Deep-brain stimulation (DBS) has been used for the treatment of medically refractory dystonia with excellent results. In this study, we compared in detail the therapeutic advantages of two DBS targets for generalized isolated dystonia. Methods: In this retrospective study, we recruited 29 patients with generalized isolated dystonia who had undergone DBS treatment targeting either the globus pallidus interna (GPi) or the subthalamic nucleus (STN) in the Department of Functional Neurosurgery at Tiantan Hospital, Beijing, China, between January 2016 and December 2021. The movement and disability subscales of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) were used to assess the severity of their dystonic symptoms and their activities of daily living, respectively. SF-36 was used to evaluate the patients' health-related quality of life. Results: The percentage improvement in the BFMDRS-M score at 6 months relative to the baseline score was clearly higher in the STN group (63.91%) than in the GPi group (38.36%). At the 3-, 6-, and 12-month follow-ups, the percentage improvement in arm symptoms was significantly higher after DBS of the STN (70.64%, 80.66%, and 76.89%, respectively) than after stimulation of the GPi (36.75%, 34.21%, and 38.47%, respectively). At 12 months after surgery, patient quality of life had improved on all SF-36 subscales in both groups. Conclusions: STN-DBS may have more advantages than GPi-DBS in patients with obvious arm dystonia. STN-DBS had a better clinical effect than GPi-DBS within 6 months after surgery.

#2

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region.

Arquivos de neuro-psiquiatria2023 Mar

Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients. A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. MéTODOS:  A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00–98,00) e 20,60 ± 7,80 (13,00–32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). CONCLUSãO:  Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

#3

Long-Term Outcome of Subthalamic Deep Brain Stimulation for Generalized Isolated Dystonia.

Neuromodulation : journal of the International Neuromodulation Society2023 Dec

Few studies have focused on subthalamic nucleus deep brain stimulation for refractory isolated dystonia, and the long-term outcomes are unclear. In this study, we evaluated the efficacy of subthalamic stimulation for generalized isolated dystonia for more than five years and explored the factors predicting clinical outcomes. A total of 16 patients with generalized isolated dystonia underwent a two-phase procedure for stimulation system implantation. After implanting the leads, we performed a test stimulation and observed the stimulation response. The severity of dystonia was assessed using a blinded rating of the Burke-Fahn-Marsden Dystonia Rating Scale based on videos recorded at scheduled times. The mean follow-up time was 7.4 ± 2.2 years (5-12.5 years). The severity of dystonia improved significantly one year after surgery. The movement score decreased from 49.3 (40.9) points at baseline to 26.5 (43.5) points (-44.6%) at six months, 12.0 (22.5) points (-66.8%) at one year, 11.25 (17.6) points (-72.7%) at three years, and 12.5 (21.0) points (-72.6%) at the last follow-up. The improvement in motor symptoms resulted in a corresponding improvement in activities of daily living. Greater long-term outcomes were correlated with early stimulation responses, lower baseline movement scores, and female sex. When analyzed comprehensively, only the baseline movement score had meaningful predictive value for the outcome. Our results indicate that subthalamic stimulation is effective and durable in treating generalized isolated dystonia. The subthalamic nucleus may be an alternative target for the treatment of refractory dystonia. Patients with less severe motor symptoms may benefit more from this treatment.

#4

Long term perceptions of illness and self after Deep Brain Stimulation in pediatric dystonia: A narrative research.

European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society2020 May

Deep Brain Stimulation (DBS) is increasingly used in pediatric patients affected by isolated dystonia, with excellent results. Despite well documented long-term effects on motor functioning, information on quality of life and social adaptation is almost lacking. The present study aims to explore the experience of illness and the relation with the device in adult patients suffering from dystonia who underwent DBS surgery in pediatric age. A narrative inquiry approach was used to collect patients' narratives of their experience with dystonia and DBS stimulator. A written interview was administered to 8 patients over 18 years old with generalized isolated dystonia who had undergone pallidal DBS implantation in childhood. A thematic analysis was realized to examine the narratives collected. Five main themes emerged: "relationship with the disease", "experience related to DBS procedure", "relationship with one's own body", "fears", "thoughts about future". Despite a general satisfaction in relation to DBS intervention, some patients expressed difficulties, such as the acceptance of changes in one's own body, concerns and fears regarding the device and the future, also considering the critical phase of transition from childhood to adulthood. These results suggest that further research is needed to understand the contribution of psychological, as much as medical, aspects to the overall outcome of the intervention. The present explorative study encourages a deeper investigations of psychological aspects of patients, in order to plan a tailored care path and to decide whether to suggest a psychological support, both before and after the intervention.

#5

Minimal Clinically Important Differences for Burke-Fahn-Marsden Dystonia Rating Scale and 36-Item Short-Form Health Survey.

Movement disorders : official journal of the Movement Disorder Society2020 Jul

Although an increasing number of trials are reported on the treatment of generalized or segmental isolated dystonia, the minimal clinically important difference thresholds for the most frequently reported outcome measures are still undetermined. To estimate the minimal clinically important difference for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey in generalized or segmental dystonia. A total of 898 paired examinations of 198 consecutive patients, aged >18 years, with idiopathic and inherited (torsin family 1 member A positive) segmental and generalized isolated dystonia were analyzed. To calculate the minimal clinically important difference thresholds, both anchor- and distribution-based methods were used simultaneously. Any improvement >16.6% or worsening larger than 21.5% on the Burke-Fahn-Marsden Dystonia Rating Scale indicates a minimal, yet clinically relevant, change. Threshold values for the Burke-Fahn-Marsden Dystonia Disability Scale were 0.5 points for both decline and improvement. Cut-off scores for the Physical Component Summary, the Mental Component Summary, and the Global (Total or Overall) Score of the 36-Item Short-Form Health Survey were 5.5 and 5.5, 6.5 and 7.5, and 7.5 and 8.5 points for clinically meaningful improvement and deterioration, respectively. The minimal clinically important difference represents the smallest change in an outcome measure that is meaningful to patients. Our estimates for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey may allow more reliable judgment of the clinical relevance of different treatments for segmental and generalized isolated dystonia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Doenças relacionadas

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Referências e fontes

Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. Pallidal Versus Subthalamic Deep-Brain Stimulation for Generalized Isolated Dystonia: A Retrospective Study.
    Journal of clinical medicine· 2024· PMID 39201044mais citado
  2. Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region.
    Arquivos de neuro-psiquiatria· 2023· PMID 37059436mais citado
  3. Long-Term Outcome of Subthalamic Deep Brain Stimulation for Generalized Isolated Dystonia.
    Neuromodulation : journal of the International Neuromodulation Society· 2023· PMID 36028445mais citado
  4. Long term perceptions of illness and self after Deep Brain Stimulation in pediatric dystonia: A narrative research.
    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society· 2020· PMID 32147411mais citado
  5. Minimal Clinically Important Differences for Burke-Fahn-Marsden Dystonia Rating Scale and 36-Item Short-Form Health Survey.
    Movement disorders : official journal of the Movement Disorder Society· 2020· PMID 32441447mais citado

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:376724(Orphanet)
  2. MONDO:0000476(MONDO)
  3. Distonia e Espasticidade(PCDT · Ministério da Saúde)
  4. GARD:21618(GARD (NIH))
  5. Variantes catalogadas(ClinVar)
  6. Busca completa no PubMed(PubMed)
  7. Q55787935(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar

Distonia isolada generalizada
Compêndio · Raras BR

Distonia isolada generalizada

ORPHA:376724 · MONDO:0000476
🇧🇷 Brasil SUS
Geral
MedGen
UMLS
C5681147
Repurposing
1 candidato
procyclidineacetylcholine receptor antagonist
EuropePMC
Wikidata
Papers 10a
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