Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent years have seen many advances in our understanding of the genetics of the dystonias, with 13 loci identified to date. The DYT1 gene, which causes most cases of childhood-onset generalized primary dystonia, was cloned in 1997, and use of cell models has begun to unravel the role of its protein (torsinA) in both health and disease. Treatment of more severe dystonia has been a difficult area, with only limited success from medical therapies. Recently, there has been increasing interest in the use of globus pallidus deep brain stimulation and a number of reports have shown promising results.
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PMID:Dystonia: an update on genetics and treatment. 1147 Sep 63

We report on monozygotic male twins of German origin with early onset cervical dystonia. No other family members were affected. Although identical in age of onset and clinical course, there were phenotypic variations. While the second-born, more affected twin suffered from a symmetric retrocollis, the twin brother mainly presented with a spasmodic torticollis to the left. Dystonia remained focal in both siblings. A DYT1 gene deletion was excluded. Including our patients, hitherto only four twin pairs with idiopathic dystonia have been reported. Although dystonia in twins can be remarkably uniform in some cases, major differences in terms of disease progression, remissions, and disability may be found. These observations underline the role of inheritance in the pathogenesis of idiopathic dystonia but also indicate that some other factors contribute to the clinical presentation of dystonia.
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PMID:Cervical dystonia in monozygotic twins: case report and review of the literature. 1221 Aug 93

The dystonias are a common clinically and genetically heterogeneous group of movement disorders. More than ten loci for inherited forms of dystonia have been mapped, but only three mutated genes have been identified so far. These are DYT1, encoding torsin A and mutant in the early-onset generalized form, GCH1 (formerly known as DYT5), encoding GTP-cyclohydrolase I and mutant in dominant dopa-responsive dystonia, and TH, encoding tyrosine hydroxylase and mutant in the recessive form of the disease. Myoclonus-dystonia syndrome (MDS; DYT11) is an autosomal dominant disorder characterized by bilateral, alcohol-sensitive myoclonic jerks involving mainly the arms and axial muscles. Dystonia, usually torticollis and/or writer's cramp, occurs in most but not all affected patients and may occasionally be the only symptom of the disease. In addition, patients often show prominent psychiatric abnormalities, including panic attacks and obsessive-compulsive behavior. In most MDS families, the disease is linked to a locus on chromosome 7q21 (refs. 11-13). Using a positional cloning approach, we have identified five different heterozygous loss-of-function mutations in the gene for epsilon-sarcoglycan (SGCE), which we mapped to a refined critical region of about 3.2 Mb. SGCE is expressed in all brain regions examined. Pedigree analysis shows a marked difference in penetrance depending on the parental origin of the disease allele. This is indicative of a maternal imprinting mechanism, which has been demonstrated in the mouse epsilon-sarcoglycan gene.
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PMID:Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome. 1152 94

A review of functional surgery for dystonia is presented. Recently renewed interest in stereotaxy for dystonia has followed the resurgence of pallidotomy and the introduction of deep brain stimulation (DBS) in Parkinson's disease (PD) in the early 1990s. However, even since the 1950s, small series of patients treated with ablative surgery have been carefully studied, providing useful information, notably regarding the tolerability of surgery. In the setting of dystonia, thalamotomy was first performed with substantial benefits, but some authors outlined the great variability in outcome, and the high incidence of operative side-effects. In the 'modern' era of functional surgery for movement disorders, the globus pallidus internus (GPi) has emerged to be currently the best target for dystonia, based on small series of patients published in the last few years. Both bilateral posteroventral pallidotomy (PVP) and bilateral pallidal stimulation, performed by several teams, have benefited a variety of patients with severe dystonia, the most dramatic improvements being seen in primary dystonia with a mutation in the DYT1 gene. Whereas patients with secondary dystonia have often shown a lesser degree of improvement, some publications have nevertheless reported major benefit. There is today a strong need for carefully controlled studies comparing secondary and primary dystonia, DYT1 and non-DYT1 dystonia, ablative surgery and DBS, with additional assessment of neuropsychological changes, especially in children treated with bilateral pallidal procedures.
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PMID:Review of the functional surgical treatment of dystonia. 1155 2

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 in the DYT1 gene is responsible for most cases of autosomal dominant early-onset PTD. We analysed the DYT1 mutation in 50 patients from a Serbian population, selected according to the proposed guidelines for diagnostic testing: (a) 38 patients with PTD onset < 26 years, and (b) 12 patients with the disease onset +/- 26 years, but with at least one affected family member with early-onset dystonia. Only three apparently sporadic patients among the 50 individuals tested were positive for the GAG deletion in the DYT1 gene: one with typical, generalized, one with long-lasting, non-progressive segmental, and one with multifocal dystonia. Molecular analysis of relatives in 2 families revealed that the lack of family history was due to reduced penetrance.
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PMID:DYT1 mutation in primary torsion dystonia in a Serbian population. 1175 56

A mutation of the DYT1 gene, which codes for torsinA, has been identified as the cause of one form of autosomal dominantly inherited dystonia. TorsinA immunohistochemistry was used to examine a case of DYT1, and several cases of non-DYT1, dystonia. No evidence was found for alterations of immunoreactivity at the light microscopic level, specifically neither cytoplasmic aggregations nor colocalization of torsinA immunoreactivity with a marker for endoplasmic reticulum. These findings contrast with results of recent cell culture studies of torsinA.
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PMID:TorsinA immunoreactivity in brains of patients with DYT1 and non-DYT1 dystonia. 1178 16

We describe a 71-year-old woman who presented to the neurology department late in life with a jerky axial dystonia due to the DYT1 GAG deletion. She recalled that her symptoms began 62 years prior to study and remained unchanged for 40 years, illustrating the broad phenotype of DYT1 idiopathic torsion dystonia.
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PMID:Late-onset axial jerky dystonia due to the DYT1 deletion. 1183 64

Dystonias are a heterogeneous group of disorders which are known to have a strong inherited basis. This review details recent advances in our understanding of the genetic basis of dystonias, including the primary dystonias, the 'dystonia-plus' syndromes and heredodegenerative disorders. The review focuses particularly on clinical and genetic features and molecular mechanisms. Conditions discussed in detail include idiopathic torsion dystonia (DYT1), focal dystonias (DYT7) and mixed dystonias (DYT6 and DYT13), dopa-responsive dystonia, myoclonus dystonia, rapid-onset dystonia parkinsonism, Fahr disease, Aicardi-Goutieres syndrome, Hallervorden-Spatz syndrome, X-linked dystonia parkinsonism, deafness-dystonia syndrome, mitochondrial dystonias, neuroacanthocytosis and the paroxysmal dystonias/dyskinesias.
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PMID:The genetics of primary dystonias and related disorders. 1191 6

When primary torsion dystonia is caused by a GAG deletion in the TOR1A gene (DYT1 dystonia), it typically presents with an early-onset dystonia involving distal limbs, subsequently spreading to a generalized dystonia. We describe a large family with an unusually broad variability in the clinical features of their dystonia both with regard to severity and age of onset. The proband of this family succumbed in his second decade to malignant generalized dystonia, whereas other family members carrying the same mutation are either asymptomatic or display dystonia that may be focal, segmental, multifocal, or generalized in distribution. One family member had onset of her dystonia at age 64 years, probably the oldest reported in genetically confirmed DYT1 dystonia. We conclude that marked phenotypic heterogeneity characterizes some families with DYT1 dystonia, suggesting a role for genetic, environmental, or other modifiers. These findings have implications for genetic testing and counseling.
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PMID:Intrafamilial phenotypic variability of the DYT1 dystonia: from asymptomatic TOR1A gene carrier status to dystonic storm. 1192 Nov 21

We report on an Italian kindred with adult-onset primary torsion dystonia (PTD). A detailed clinical examination of the six definitely affected family members revealed a mild, purely focal phenotype. The disease involved only one body part (eyes, neck, or arm). PTD in this family was not linked to the known disease loci (DYT1, DYT6, DYT7, and DYT13), and the 3-bp deletion in the DYT1 gene was also excluded. These findings support genetic heterogeneity of PTD and indicate that a novel unassigned gene is responsible for focal dystonia in this family.
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PMID:Novel Italian family supports clinical and genetic heterogeneity of primary adult-onset torsion dystonia. 1192 Nov 30


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