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)

To study gene loci and disease phenotypes, 18 families with dominant OPCA were subjected for linkage analysis to SCA1- or SCA2-linked microsatellites. Total individuals consisted of 190. Among them, 77 were affected. Consequently, 10 families were 6p-linked, 7 were 12q-linked, and one was type-undetermined. These results indicate that the majority of dominant OPCA in Japan are composed with these two genotypes. Clinically, these two disorders show progressive ataxia, Babinski reflexes, and terminal amyotrophy. Other common features in SCA1 were hyperreflexia, spasticity, mild nystagmus at early stage, slow saccade, and external ophthalmoparesis (EOP) at advanced stage. In contrast SCA2 showed progressive hyporeflexia and slow saccade from early stage. Moreover, choreiform movement, tremor, and rhythmic myoclonus were more frequent in the latter. Neuropathologically, dentate nucleus, brainstem motor nuclei, spinocerebellar tract were involved more severely in SCA1 than SCA2. Degeneration of substantia nigra is more marked in SCA2 than SCA1. These observations strongly indicate that there are correlations between genotypes and phenotypes in dominant OPCAs. Conversely, it is possible to diagnose these two genetic disorders from the clinico-pathological findings.
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PMID:[Linkage study of hereditary spinocerebellar ataxia, and probable correlation for the loci to the disease phenotypes]. 817 26

Seventy-seven families with autosomal dominant cerebellar ataxia were analyzed for the CAG repeat expansions causing spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. The SCA1 mutation accounted for 9%, SCA2 for 10%, SCA3 for 42%, and SCA6 for 22% of German ataxia families. Seven of 27 SCA6 patients had no family history of ataxia. Age at onset correlated inversely with repeat length in all subtypes. Yet the average effect of one CAG unit on onset age was different for each SCA subtype. We compared clinical, electrophysiological, and magnetic resonance imaging (MRI) findings to identify phenotypic characteristics of genetically defined SCA subtypes. Slow saccades, hyporeflexia, myoclonus, and action tremor proposed SCA2. SCA3 patients frequently developed diplopia, severe spasticity or pronounced peripheral neuropathy, and impaired temperature discrimination, apart from ataxia. SCA6 presented with a predominantly cerebellar syndrome and patients often had onset after 55 years of age. SCA1 was characterized by markedly prolonged peripheral and central motor conduction times in motor evoked potentials. MRI scans showed pontine and cerebellar atrophy in SCA1 and SCA2. In SCA3, enlargement of the fourth ventricle was the main sequel of atrophy. SCA6 presented with pure cerebellar atrophy on MRI. However, overlap between the four SCA subtypes was broad.
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PMID:Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? 940 86

We report on a 30-year-old patient with advanced cerebellar degeneration due to SCA2. He presented with severe myoclonus, which was resistant to conventional therapy and dramatically improved after administration of 12-18 gm/die piracetam. Piracetam may be considered in the treatment of refractory myoclonus in spinocerebellar degenerations.
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PMID:Suppression of myoclonus in SCA2 by piracetam. 1614 96

Hereditary spinocerebellar ataxia (SCA) is a cluster of heterogeneous disorders. At now, 29 dominant loci have been assigned. Responsible genes and mutations are determined in at least 14 of them. In recessive and X-linked SCAs, 15 loci have been mapped, and mutation in each gene is determined by 6 disorders. Molecular mechanism of those SCAs are variable. Generally, deletion, insertion, or substitution in a gene modifies the primary structure of mRNA, subsequently resulting in disturbance of transcription or in translation of mutant proteins showing loss-of-function or dominant negative effect. Large expansion of tandem repeat in promotor region or intron suppress translation of the gene, thus causing similar effect. Expansion of (CAG)n in coding exon is translated into proteins containing elongated poly-Q. Since the poly-Q fragment is cytotoxic, this kind of mutation causes protein toxic gain-of-function. In addition, RNA toxic gain-of-function mechanism recently gains attention as a new molecular mechanism of SCA8 and SCA10. Clinically, dominant SCA with dynamic mutation shows variable onset of age, severity, and variation of clinical phenotypes. Among this clinical complexity, vocal cord abductor paralysis in SCA1, familial parkinsonism in SCA2, vestibular dysfunction and axonal neuropathy in MJD, and axial myoclonus in SCA14, are reviewed for potential usefulness in clinical practice.
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PMID:[Clinical feature and molecular genetics of hereditary spinocerebellar ataxia]. 1821 Aug 1

Autosomal dominant spinocerebellar ataxias (SCAs) can present with a large variety of noncerebellar symptoms, including movement disorders. In fact, movement disorders are frequent in many of the various SCA subtypes, and they can be the presenting, dominant, or even isolated disease feature. When combined with cerebellar ataxia, the occurrence of a specific movement disorder can provide a clue toward the underlying genotype. There are reasons to believe that for some coexisting movement disorders, the cerebellar pathology itself is the culprit, for example, in the case of cortical myoclonus and perhaps dystonia. However, movement disorders in SCAs are more likely related to extracerebellar pathology, and imaging and neuropathological data indeed show involvement of other parts of the motor system (substantia nigra, striatum, pallidum, motor cortex) in some SCA subtypes. When confronted with a patient with an isolated movement disorder, that is, without ataxia, there is currently no reason to routinely screen for SCA gene mutations, the only exceptions being SCA2 in autosomal dominant parkinsonism (particularly in Asian patients) and SCA17 in the case of a Huntington's disease-like presentation without an HTT mutation.
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PMID:Movement disorders in spinocerebellar ataxias. 2202 Nov 60