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)

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

The authors report a kindred in which GTP-CH deficiency resulted in a myoclonus-dystonia syndrome. The proband, a 17-year-old boy, presented with early-onset myoclonus and later, dystonia and bradykinesia. Blood prolactin was increased and CSF homovanillic acid, 5-hydroxyindoleacetic acid, and biopterin were all reduced. L-Dopa/carbidopa administration resulted in clinical improvement. In the paternal branch, the grandfather and three relatives had myoclonus-dystonia and resting or postural tremor of limbs. The authors found a missense mutation in the exon 6 of GCH-1 gene (K224R).
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PMID:Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome. 1239 38

Dystonia-plus syndromes represent a heterogeneous group of diseases, where dystonia is accompanied by other neurological features and gene mutations can be detected frequently. Symptomatic dystonias and complex neurodegenerative diseases with dystonia as part of the clinical presentation are excluded from this category. At present, the following disorders are categorized as dystonia-plus syndromes: Dopa-responsive dystonia (DRD) is a mostly pediatric-onset, neurometabolic disorder with two different modes of inheritance: in its autosomal-dominant form, heterozygous mutations of GTP-cyclohydrolase I (GCH1, DYT5) cause DRD with reduced penetrance and excellent and lasting response to levodopa. Autosomal-recessive (AR) forms of DRD are caused by homozygous or compound heterozygous mutations of the tyrosine hydroxylase (TH) or the sepiapterin reductase (SPR) gene. In AR-DRD, the phenotype is generally more severe including cognitive deficits and developmental delay. Diagnosis can be confirmed by analysis of CSF pterine metabolites. Alternatively, comprehensive genetic testing yields causative mutations in up to 80% of patients. Myoclonus-dystonia (M-D) is caused by heterozygous mutations of the epsilon-sarcoglycan gene (SGCE). Dystonia is generally only mild to moderate, and 'lightning-like' myoclonic jerks occur rarely at rest and can be triggered by complex motor tasks like writing and drawing. Both features together with an age at onset below 25 years strongly predict SGCE mutation in M-D and differentiate this genetic disease from other 'jerky' dystonias. The combination of dystonia and parkinsonism can only be rarely observed in non-degenerative syndromes. Besides DRD, two additional syndromes have been classified. Rapid-onset dystonia-parkinsonism (RPD, DYT12) is a rare disorder with an abrupt onset of symptoms over minutes to days, prominent bulbar involvement and parkinsonism with a lack of response to levodopa. Patients with this rare phenotype should be screened for mutation in the Na(+)/K(+) ATPase alpha3-subunit (ATP1A3) gene, even if family history is negative. Recently, a novel form of dystonia-parkinsonism (DYT16) has been found to be linked to mutations in the PRKRA gene, whose relation to basal ganglia disorders is yet unknown .
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PMID:Dystonia-plus syndromes. 2059 Aug 7

Myoclonus dystonia syndrome (MDS) refers to a group of heterogeneous nondegenerative clinical conditions characterized by the association of myoclonus and dystonia as the only or prominent symptom. The "core" of MDS is represented by inherited myoclonus-dystonia (M-D), a disorder with autosomal-dominant inheritance and reduced penetrance, beginning in early childhood with a relatively benign course, with myoclonus as the most predominant and disabling symptom. Alcohol responsiveness and psychiatric symptoms are characteristic features. Mutations in the epsilon-sarcoglycan gene (SGCE, DYT11) represent the major genetic cause, but M-D is genetically heterogeneous. In a variable proportion of M-D patients no mutation is found, and at least one other locus (DYT15) has been linked to the disease. Patients with primary dystonia, with or without the DYT1 mutation, may show irregular and arrhythmic jerky movements associated with dystonia. Usually dystonia is the prominent symptom and the myoclonic jerk involves the same body region; this condition, currently defined as "myoclonic dystonia," is included in the spectrum of MDS. Dopa-responsive dystonia due to mutation in the GTP-CH gene and vitamin E deficiency can present with a phenotype of dystonia and myoclonus in combination; both conditions should be considered in the diagnostic approach to patients since they are potentially treatable.
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PMID:Myoclonus-dystonia syndrome. 2149 8