Unusual Early-Onset Huntington's Disease

Vargas, Antônio Pedro; Carod-Artal, Francisco Javier; Bomfim, D.; Vázquez-Cabrera, Carolina Benigna; Dantas‐Barbosa, Carmela

doi:10.1177/08830738030180061301

Cited by 15 publications

(14 citation statements)

References 17 publications

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“…Although both the early- and adult-onset forms of HD are characterized by dementia, movement disorder, and personality changes, juvenile HD patients do not display chorea as adult-onset patients. Instead, juvenile HD patients are often rigid and stiff and exhibit severe cognitive dysfunction and seizure that is not seen in adult HD patients (Vargas et al, 2003; Squitieri et al, 2006). In the brains of juvenile HD patients, there are more nuclear aggregates and fewer neuropil aggregates than in adult HD brains (DeFiglia et al, 1997; Gutekunst et al, 1998), and also more widespread degeneration, suggesting that polyQ repeat lengths mediate different pathogenic pathways.…”

Section: Discussionmentioning

confidence: 99%

“…There is strong evidence that in Huntington’s disease (HD), polyQ repeats larger than 60 glutamines cause juvenile cases, who display different symptoms and have more widespread degeneration in the brain. For example, juvenile HD patients do not display chorea, but they have severe cognitive dysfunction and seizure that is absent in adult HD patients (Vargas et al, 2003; Squitieri et al, 2006). Juvenile HD patient brains also have more nuclear aggregates, whereas adult HD brains have more neuripil aggregates, also suggesting that polyQ lengths mediate different pathogenic pathways (DeFiglia et al, 1997; Gutekunst et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

Huang

Guo

et al. 2015

Cell Reports

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SUMMARY In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knock-in mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

Huang

Guo

et al. 2015

Cell Reports

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“…However, this literature survey was conducted before the availability of genetic testing to confirm the diagnosis. Review of the literature revealed only 12 cases of genetically confirmed JHD with reported seizures, only 5 of which had accompanying EEG data 5–8. Seizure type, EEG findings, and response to antiepileptic drugs were highly variable across the rare published cases, and the paucity of available data precludes drawing meaningful conclusions.…”

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confidence: 99%

Seizures in juvenile Huntington's disease: Frequency and characterization in a multicenter cohort

et al. 2012

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Little is known about the epilepsy that often occurs in the juvenile form of Huntington's disease (HD), but is absent from the adult-onset form. The primary aim of this study was to characterize the seizures in juvenile HD (JHD) subjects with regard to frequency, semiology, defining EEG characteristics, and response to antiepileptic agents. A multicenter, retrospective cohort was identified by database query and/or chart review. Data on age of HD onset, primary HD manifestations, number of CAG repeats, the presence or absence of seizures, seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic drugs (AEDs), and EEG results were assembled, where available. Ninety subjects with genetically confirmed JHD were included. Seizures were present in 38% of subjects and were more likely to occur with younger ages of HD onset. Generalized tonic-clonic seizures were the most common seizure type, followed by tonic, myoclonic, and staring spells. Multiple seizure types commonly occurred within the same individual. Data on EEG findings and AED usage are presented. Seizure risk in JHD increases with younger age of HD onset. Our ability to draw firm conclusions about defining EEG characteristics and response to AEDs was limited by the retrospective nature of the study. Future prospective studies are required.

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“…A evolução cursa com piora do quadro cognitivo, psiquiátrico e com surgimento de sintomatologia motora 4,7 . A família também pode relatar como primeiros sintomas motores dificuldade de deambular, quedas frequentes, bem como disartria 6,12,20,21,22 . A instabilidade postural em associação com quedas, sinais piramidais e regressão cognitiva pode levar ao diagnóstico diferencial de síndrome de regressão idiopática 22 .…”

Section: Dicussãounclassified

“…A família também pode relatar como primeiros sintomas motores dificuldade de deambular, quedas frequentes, bem como disartria 6,12,20,21,22 . A instabilidade postural em associação com quedas, sinais piramidais e regressão cognitiva pode levar ao diagnóstico diferencial de síndrome de regressão idiopática 22 . Também podem ocorrer convulsões sem histórico prévio 10,11,17 .…”

Section: Dicussãounclassified

Manifestações neuropsicomotoras da doença de Huntington juvenil

Nogueira

Rocha

Vasconcelos

et al. 2019

Rev. Med. (São Paulo)

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Nogueira LA, Rocha AEO, Vasconcelos LM, Figueiredo Junior JAB, Bragato SGR. Manifestações neuropsicomotoras da doença de Huntington juvenil: sinais e sintomas e achados de imagem / Neuropsychomotor manifestations of juvenile Huntington's disease: signs and symptoms and imaging findings. Rev Med (São Paulo). 2019 nov.-dez.;98(6):408-14. RESUMO: A Doença de Huntington Juvenil (DHJ) consiste na neurodegeneração de células nervosas causada pela formação da proteína alterada denominada huntingtina, acumuladano citoplasma e núcleo de neurônios, capaz de gerar morte progressiva destas células de forma mais evidente no corpo estriado, que engloba os núcleos caudado e putâmen. A variante juvenil da Doença de Huntington manifesta-se em pacientes com idades entre 0 a 20 anos, com variedade de distúrbios motores, cognitivos e comportamentais. Com o objetivo de estudar os mais prevalentes sinais, sintomas e achados de imagem, bem como as manifestações iniciais e a evolução sintomatológica ao decorrer da doença, foi realizada uma revisão integrativa de literaturas, incluindo o total de 25 artigos selecionados após a adequação de critérios de exclusão e inclusão. Após a análise dos dados, concluiu-se que os sintomas mais destacados foram rigidez muscular, disartria, convulsões, bradicinesia e disfunções cognitivas e comportamentais. Em se tratando de achados de imagem, prevaleceram atrofia de núcleos da base e cerebelo em pacientes com a doença mais avançada e diagnosticados em tempo maior.ABSTRACT: Juvenile Huntington's disease consists of neurodegeneration of nerve cells caused by the formation of the altered protein called huntingtin, accumulated in the cytoplasm and nucleus of neurons, capable of generating progressive death of these cells more clearly in the striatum, which includes the nuclei caudate and putamen. The juvenile variant of Huntington's disease manifests in patients aged 0 to 20 years, with a variety of motor, cognitive and behavioral disorders. In order to study the most prevalent signs, symptoms and imaging findings, as well as the initial manifestations and the symptomatic evolution during the course of the disease, an integrative literature review was carried out, including a total of 25 articles selected after the adequacy of criteria exclusion and inclusion. After analyzing the data, it was concluded that the most prominent symptoms were muscle stiffness, dysarthria, seizures, bradykinesia and cognitive and behavioral dysfunctions. In terms of imaging findings, atrophy of nuclei of the base and cerebellum prevailed in patients with the most advanced disease and diagnosed in greater time.

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Unusual Early-Onset Huntington's Disease

Cited by 15 publications

References 17 publications

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

Seizures in juvenile Huntington's disease: Frequency and characterization in a multicenter cohort

Manifestações neuropsicomotoras da doença de Huntington juvenil

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