Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report three members of a single family with an apparently autosomal dominant, nonparoxysmal, hyperkinetic movement disorder with onset in adolescence. The proband, a 56-year-old woman, manifested dystonia, tremor and myoclonus; one of her daughters exhibited myoclonus with tremor, and the other demonstrated myoclonus with chorea later accompanied by tremor and dystonia. The slowly progressive but not debilitating symptoms were restricted to the head, arms and hands and were only moderately affected by alcohol. Laboratory investigations failed to identify any abnormality, and linkage analysis excluded the region containing the DYT1 locus, indicating that the gene responsible for idiopathic torsion dystonia was not implicated in this family. While this disorder shares manifestations with myoclonic dystonia, essential myoclonus and benign chorea, the marked intrafamilial heterogeneity and the sex-limited phenotype expressed only in females of two generations appear to be unique.
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PMID:Intrafamilial heterogeneity of movement disorders: report of three cases in one family. 926 60

To date, at least 12 types of primary dystonia can be distinguished on a genetic basis. A 3-bp deletion in the DYT1 gene causes early onset, generalized torsion dystonia (TD), and mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes result in dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor in one large family (DYT11) has recently been implicated in myoclonus-dystonia. Furthermore, seven other loci for dystonia genes have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), three types of paroxysmal dystonia (DYT8-10), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia-parkinsonism (DYT12). No positive linkage results have yet been obtained for autosomal recessive TD (DYT2) and several other families of different types of dominantly inherited TD (DYT4). In addition, hereditary secondary dystonia may occur as part of familial diseases of the basal ganglia, metabolic and storage disorders, and various X-linked and other familial neurodegenerative syndromes affecting the basal ganglia. 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 dystonia]. 1091 37

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

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

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

Myoclonus-dystonia has recently been associated with mutations in the epsilon-sarcoglycan gene (SCGE) on 7q21. Previously, the authors reported a patient with myoclonus-dystonia and an 18-bp deletion in the DYT1 gene on 9q34. The authors have now re-evaluated the patient harboring this deletion for mutations in the SGCE gene and identified a missense change. In the current study, the authors describe the clinical details of this family carrying mutations in two different dystonia genes. Further analysis of these mutations separately and together in cell culture and in animal models should clarify their functional consequences.
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PMID:Clinical findings of a myoclonus-dystonia family with two distinct mutations. 1239 38

Myoclonus-dystonia is a movement disorder associated with mutations in the epsilon-sarcoglycan gene (SGCE) in most families and in the DRD2 and DYT1 genes in two single families. In both of the latter families, we also found a mutation of SGCE. The molecular mechanisms through which the detected mutations may contribute to myoclonus-dystonia remain to be determined.
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PMID:Epsilon-sarcoglycan mutations found in combination with other dystonia gene mutations. 1240 71

Renewed interest in stereotaxy for dystonia followed the introduction of deep brain stimulation (DBS) in Parkinson's disease and essential tremor in the 1990s. DBS evolved from ablative surgery, which was applied with varying results in the 1950s in patients with movement disorders such as Parkinson's disease, essential tremor and dystonia. The present review summarizes the current knowledge on clinical aspects of DBS in dystonia (Dec. 2002). Excellent results have been achieved in dystonic patients carrying a mutation in the DYT1 gene with improvements up to 90 %. Similar results may also be obtained in patients with idiopathic generalized dystonia, myoclonus-dystonia syndrome, and tardive dystonia. Substantial improvement has been observed in patients with focal dystonia (for instance cervical dystonia). Patients with secondary dystonia often display a lesser and more variable degree of improvement. Long-term studies are warranted to assess both motor and neuropsychological sequelae of DBS in dystonia. Furthermore, the optimal target for different dystonic disorders remains to be determined, although the globus pallidus internus has currently emerged as the most promising target for dystonia.
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PMID:Deep brain stimulation in dystonia. 1276 37

Despite clinical and genetic complexity of dystonia, knowledge of primary torsion dystonia and dystonia-plus syndromes was recently expanded. Part of the category of primary dystonia includes genetic forms (DYT1, DYT6, DYT13). The DYTI mutation, with predominant limbs (95p. 100) and neck and trunk (25-35p. 100) involvement accounts for about 80p. 100 of the early onset cases in the Ashkenazi population and of 16-53p. 100 in the non- Ashkenazi population. The dystonia-plus group is defined by the association of parkinsonism (dopa-responsive-dystonia and rapid-onset dystonia-parkinsonism) or myoclonus (myoclonus-dystonia). Dopa-responsive-dystonia is a heterogeneous group with several causes (GCH1 mutations, compound mutations in GCH1, mutations in TH gene, or in 6-PTS gene). Differential diagnosis could be juvenile parkinsonism (parkin mutations). Epsilon-sarcoglycan mutation accounts for a sub-group of myoclonus-dystonia, but other genes are still unidentified. The vast majority of dystonia are sporadic and still unexplained. Functional imaging may bring new insights in disease mechanisms. Because of phenotypic overlaps, within dystonia, new classifications based on functional markers may emerge.
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PMID:Dystonia: phenotypes and genotypes. 1462 53

Primary dystonias represent a clinically and genetically heterogeneous group of movement disorders. Mutations in the epsilon-sarcoglycan (SGCE) gene have been found recently to cause myoclonus-dystonia (MD). Considerable clinical variation of SGCE mutation carriers leads to the hypothesis that mutations in the SGCE gene might also be relevant for other subtypes of dystonias. To determine the contribution of mutations in the SGCE gene in patients with different subtypes of dystonias, we analyzed the coding sequence of the SGCE gene in a group of 296 patients with a clinical phenotype of primary dystonia and in 2 patients with a clinical phenotype of myoclonus-dystonia. Patients with mutations in the DYT1 gene were excluded. We could not detect a mutation in the SGCE gene in any of the 298 patients. Our results suggest that mutations in the SGCE gene cannot be held responsible for other subtypes of primary dystonia.
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PMID:Lack of mutations in the epsilon-sarcoglycan gene in patients with different subtypes of primary dystonias. 1539 16


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