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)

Thirty Italian patients with sporadic, early-onset, primary dystonia were screened for the DYT1 mutation. Five patients were positive (mean age at onset, 8 years); two had the typical phenotype, two a generalised dystonia also involving the cranial muscles, and one a segmental dystonia. In the other 25 patients (mean age at onset, 7.7 years), dystonia was generalised in 22 patients and remained segmental in three. Our results indicate the role of DYT1 mutation in Italian patients and confirm clinical and genetic heterogeneity of early-onset primary dystonia.
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PMID:Frequency of DYT1 mutation in early onset primary dystonia in Italian patients. 1192 Nov 34

Deep brain stimulation for severe dystonia is still in the very first stage of development. Only single case reports or small case series have been reported to date. Best results have been obtained with pallidal stimulation in patients with primary generalised dystonia, especially in DYT1 mutation carriers. In secondary dystonia, conflicting results were reported. However, there is today enough promising evidence for a striking efficacy of pallidal stimulation in dystonia, supporting the need for further investigations in the field, with collaborative projects (regarding to the limited number of eligible patients); double-blind studies, including a consensus about surgical method; and a precise anatomic analysis of the position of the electrode. A careful assessment of the efficacy by using improved clinical scale is also warranted.
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PMID:Results of deep brain stimulation for dystonia: a critical reappraisal. 1194 61

Deep brain stimulation (DBS) for dystonia still needs to be considered investigational, because there are no controlled studies for this indication, the optimal target point is uncertain, and long-term effects are unknown. The striking improvement of levodopa-induced dyskinesias in Parkinson's disease by deep brain stimulation of the internal pallidum has encouraged the use of this therapy for generalized and severe segmental dystonia in children and adults. Single case and small cohort studies have reported impressive efficacy of pallidal DBS in patients with primary dystonia, especially DYT1 mutation carriers, but results in secondary dystonia are less conclusive. This article discusses the different factors influencing patient selection for surgical treatment and describes standardized methods and the caveats for clinical documentation of treatment results in dystonia.
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PMID:Deep brain stimulation for dystonia: patient selection and evaluation. 1194 64

A study of Danish probands with primary torsion dystonia is presented. The probands were examined clinically and biochemically to exclude secondary dystonia. Mutation analyses for the GAG-deletion in the DYT1 gene were performed on 107 probands; and the mutation was detected in three. All three probands had the classical phenotype of DYT1-dystonia, but only one had a family history of dystonia. The other two probands had, obviously, sporadic DYT1-dystonia, one of which was caused by a de novo mutation, while the other one had a parent being an asymptomatic carrier. De novo mutations in the DYT1 gene are seldom reported although independent founder mutations are known to have occurred. The frequency of DYT1-dystonia was low in our study even though several probands had early onset generalised dystonia. None of the probands in our study with other types of dystonia had the GAG-deletion as reported in other studies. The difficulties in genetic counselling concerning the heterogeneity of dystonia exemplified by DYT1-dystonia are outlined.
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PMID:Inherited and de novo mutations in sporadic cases of DYT1-dystonia. 1197 27

Generalized dystonia is known as a type of movement disorder in which pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is well established for Parkinson's disease (PD) and tremor dominant movement disorders. We report on two cases of generalized dystonia which were successfully treated by chronic high frequency stimulation in the Globus pallidus internus (GPI). Two 26 and 27 years old males suffered from severe torsion dystonia and multisegmental dystonia of the lower limbs. Case 1 is a familiar type of dystonia (DYT1 positive). The onset of symptoms in both cases was at age 7. The complaints were initially treated with orally administered benzodiazepines, anticholinergic drugs, later by baclofen and L-DOPA. However there was no response. Case 2 was a patient with a history of left side dominated dystonia since the age of 8. It was first diagnosed as a psychogenic movement disorder. Prior to surgery he was treated with L-DOPA, anticholinergics, Baclofen without any effect. There was only a limited effect on high doses of diazepam. The patient is DYT1 negative. The target point was on both sides the GPI. Intraoperative computerized tomography (CT) and ventriculography (VG) were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode position. Surgery was performed under analgosedation. Two weeks after surgery we first observed a relief of symptoms in both cases. A significant reduction in the Burke-Fahn-Marsden-Dystonia Movement Rating Scale was observed at the 6 month follow-up (case 1: 95%, case 2: 80%). In case 1 a slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The medication was continuously reduced. At the 24 month follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (mean 3.5 V, 400 microseconds, 145 Hz).
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PMID:Deep brain stimulation of the globus pallidus internus (GPI) for torsion dystonia--a report of two cases. 1197 95

The controversy regarding the mode of inheritance of idiopathic torsion dystonia in the Ashkenazi Jewish population has been resolved. At one time it was believed to be inherited as an autosomal recessive disorder. But recent studies, including a prospective, systematic, blinded analysis of the first- and second-degree relatives of 43 probands with age at onset less than 28 years found the disorder to be inherited in an autosomal dominant manner with a penetrance of approximately 0.30. Linkage analysis of Ashkenazi Jewish families with multiple affected members revealed that the gene for dystonia in this population is located in the q34 region of chromosome 9. This is the same region found to encode the dominant DYT1 gene for dystonia in a large non-Jewish family with a penetrance of about 0.70. It is likely that the disorder in these two ethnic populations may be caused by the same locus, and that the difference in penetrance may reflect different mutations operating in these two populations. We have found no evidence for genetic heterogeneity in the Ashkenazi Jewish families studied for linkage analysis, but there is at least one non-Jewish family with idiopathic torsion dystonia that is not linked to this region. Allelic association in 9q34 in the Ashkenazi Jewish population has narrowed the dystonia gene to a region of less than 2 cM.
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PMID:The genetics of idiopathic torsion dystonia. 1198 65

Dystonia is not uncommon in childhood, and identification of its etiology is an ultimate aim in the clinical evaluation of dystonia. Advances in neuroimaging, recent identification of gene or loci implicated in dystonic syndromes, and characterisation of new pathological entities (creatine deficiency, biotin-responsive basal ganglia disease) enlarge our understanding of childhood dystonia, and expend its diagnosis spectrum. Awareness of the diverse etiologic categories of childhood-onset dystonia is necessary to accurate diagnosis approach. Clinical examination and cerebral magnetic resonance imaging are the keys of this diagnosis approach. Primary dystonia is defined as syndromes in which dystonia is the sole phenotypic manifestation (especially no cognitive deterioration is observed, and brain MRI is normal); DYT1 dystonia, in which the abnormal gene is located on chromosome 9, is the most frequent childhood-onset primary dystonia; progressive generalisation of the abnormal movements occur in 70p.cent of the patients. Dopa - Responsive Dystonia are characterized by marked diurnal fluctuations of the dystonic symptoms and by their marked and sustained response to dopaminergic therapy; associated parkinsonian signs are usually observed later in the course of the disease. Clinical presentation of DRD might be atypical (mimicking cerebral palsy or isolated limb pain without diurnal fluctuation). DRD is rare, but a trial of L-dopa should be performed on all patients with childhood-onset dystonia, lasting at least one month. Secondary dystonias or heredodegenerative diseases are the most frequent etiology of childhood-onset dystonic syndromes. Among a huge range of heredodegenerative disease, those that are amenable to a specific treatment, such as Wilson's disease or creatine deficiency, should be particularly investigated. The main objective of investigation of dystonia is to identify secondary dystonias or heredodegenerative diseases. Further investigations will be performed according to the clinical characteristics of the dystonia, to the presence of associated neurological or extraneurological symptoms, and according to brain imaging; this approach must be discussed for each single patient. The aim of the diagnosis strategy is the rapid identification of the etiology of dystonia which will lead to accurate treatment and pertinent genetic counselling.
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PMID:[The varied etiologies of childhood-onset dystonia]. 1198 83

Indices of dopamine transmission were measured in the postmortem striatum of DYT1 dystonia brains. A significant increase in the striatal 3,4-dihydroxyphenylacetic acid/dopamine ratio was found. Quantitative autoradiography revealed no differences in the density of dopamine transporter or vesicular monoamine transporter-2 binding; however, there was a trend toward a reduction in D(1) receptor and D(2) receptor binding. One brain with DYT1 parkinsonism was similarly evaluated and marked reductions in striatal dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid content as well as the density of binding of all four dopaminergic ligands were measured.
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PMID:Dopamine transmission in DYT1 dystonia: a biochemical and autoradiographical study. 1217 84

Currently, at least 12 types of dystonia can be distinguished on a genetic basis. Advances in the molecular genetics of dystonia have led to the recent identification of a 3-bp deletion in the DYT1 gene, causing early-onset generalized torsion dystonia (TD), and to the detection of mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes causing dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor has been shown to be associated with myoclonus-dystonia in one family. In addition, six other dystonia gene loci have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), two types of paroxysmal dystonia (DYT8, DYT9), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia parkinsonism (DYT12). No positive linkage studies have as yet been reported for autosomal recessive TD (DYT2) and in several other large families with various types of dominantly inherited TD (DYT4). It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders.
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PMID:Genetics of primary dystonia. 1219 83

The neuropathology of the primary dystonias is not well understood. We examined brains from identical twins with DYT1-negative, dopa-unresponsive dystonia. The twins exhibited mild developmental delays until age 12 years when they began developing rapidly progressive generalized dystonia. Genetic, metabolic, and imaging studies ruled out known causes of dystonia. Cognition was subnormal but stable until the last few years. Death occurred at ages 21 and 22 years. The brains were macroscopically unremarkable. Microscopic examination showed unusual glial fibrillary acidic protein-immunoreactive astrocytes in multiple regions and iron accumulation in pallidal and nigral neurons. However, the most striking findings were 1) eosinophilic, rod-like cytoplasmic inclusions in neocortical and thalamic neurons that were actin depolymerizing factor/cofilin-immunoreactive but only rarely actin-positive; and 2) abundant eosinophilic spherical structures in the striatum that were strongly actin- and actin depolymerizing factor/cofilin-positive. Electron microscopy suggested that these structures represent degenerating neurons and processes; the accumulating filaments had the same dimensions as actin microfilaments. To our knowledge, aggregation of actin has not been reported previously as the predominant feature in any neurodegenerative disease. Thus, our findings may shed light on a novel neuropathological change associated with dystonia that may represent a new degenerative mechanism involving actin, a ubiquitous constituent of the cytoskeletal system.
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PMID:Aggregation of actin and cofilin in identical twins with juvenile-onset dystonia. 1232 76


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