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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. The clinical symptoms include cerebellar dysfunction and associated signs from dysfunction in other parts of the nervous system. So far, five spinocerebellar ataxia (SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7. Loci for SCA4 and SCA5 have been mapped. However, approximately one-third of SCAs have remained unassigned. We have identified a Mexican American pedigree that segregates a new form of ataxia clinically characterized by gait and limb ataxia, dysarthria, and nystagmus. Two individuals have seizures. After excluding all known genetic loci for linkage, we performed a genomewide search and identified linkage to a 15-cM region on chromosome 22q13. A maximum LOD score of 4.3 (recombination fraction 0) was obtained for D22S928 and D22S1161. This distinct form of ataxia has been designated "SCA10." Anticipation was observed in the available parent-child pairs, suggesting that trinucleotide-repeat expansion may be the mutagenic mechanism.
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PMID:Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. 997 98

The autosomal dominant spinocerebellar ataxias (SCA) are a heterogeneous group of degenerative diseases presenting with ataxic gait, limbs ataxia, dysarthria and cerebellar oculomotor disturbances. Usually, cerebellar signs are associated with pyramidal signs, extra-pyramidal signs, spinal signs and signs of peripheral neuropathy. Neuropathological studies have disclosed an involvement of the cerebellum and its afferent/efferent pathways, of the brainstem and of the spinal cord. Distinct entities are now recognized: SCA1, SCA2, SCA3/Machado-Joseph disease, SCA4, SCA5,SCA6, SCA7 and dentatorubropillidoluysian atrophy (DRPLA). In most cases, a CAG trinucleotide repeat expansion has been demonstrated by genetic investigations. Moreover, recent studies have shown that autosomal dominant spinocerebellar ataxias are characterized by intra-nuclear inclusions containing polyglutamine in affected cells. These complexes might pl ay a determinant role in the neurodegenerative process. Cell death could be due to accumulation of a polyglutamine as a result of trinucleotide repeats.
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PMID:[Autosomal dominant spinocerebellar ataxia]. 1067 73

The autosomal dominant cerebellar ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of disorders. Ten responsible genes have been identified for spinocerebellar ataxia types SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA12 and SCA17, and dentatorubral pallidoluysian atrophy (DRPLA). The mutation is caused by an expansion of a CAG, CTG or ATTCT repeat sequence of these genes. Six additional loci, SCA4, SCA5, SCA11, SCA13, SCA14 and SCA16 have also been mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic aetiologies of at least 20% of ADCA have yet to be elucidated. We ascertained and clinically characterized a four-generation Chinese pedigree segregating an autosomal dominant phenotype for cerebellar ataxia. Direct mutation analysis, linkage analysis for all known SCA loci and a genome-wide linkage study were performed. Direct mutation analysis excluded SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA, and genetic linkage analysis excluded SCA4, 5, 11, 13, 14 and 16. The genome-wide linkage study suggested linkage to a locus on chromosome 1p21-q23, with the highest two-point LOD score at D1S1167 (Zmax = 3.46 at theta = 0.00). Multipoint analysis and haplotype reconstruction traced this novel SCA locus (SCA22) to a 43.7-cM interval flanked by D1S206 and D1S2878 (Zmax = 3.78 under four liability classes, and 2.67 using affected-only method). The age at onset ranged from 10 to 46 years. All affected members had gait ataxia with variable features of dysarthria and hyporeflexia. Head MRI showed homogeneous atrophy of the cerebellum without involvement of the brainstem. In six parent-child pairs, median onset occurred 10 years earlier in offspring than in their parents, suggesting anticipation. This family is distinct from other families with SCA and is characterized by a slowly progressive, pure cerebellar ataxia.
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PMID:A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. 1467 32

Spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of disorders. Current molecular classification corresponds to the order of gene description (SCA1-SCA 25). The prevalence of SCAs is estimated to be 1-4/100,000. Patients exhibit usually a slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and/or ataxic gait. They can present also with pigmentary retinopathy, extrapyramidal movement disorders (parkinsonism, dyskinesias, dystonia, chorea), pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioral symptoms), peripheral neuropathy. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. The following clinical features have some specific values for predicting a gene defect: slowing of saccades in SCA2, ophthalmoplegia in SCA1, SCA2 and SCA3, pigmentary retinopathy in SCA7, spasticity in SCA3, dyskinesias associated with a mutation in the fibroblast growth factor 14 (FGF 14) gene, cognitive impairment/behavioral symptoms in SCA17 and DRPLA, seizures in SCA10, SCA17 and DRPLA, peripheral neuropathy in SCA1, SCA2, SCA3, SCA4, SCA8, SCA18 and SCA25. Neurophysiological findings are compatible with a dying-back axonopathy and/or a neuronopathy. Three patterns of atrophy can be identified on brain MRI: a pure cerebellar atrophy, a pattern of olivopontocerebellar atrophy, and a pattern of global brain atrophy. A remarkable observation is the presence of dentate nuclei calcifications in SCA20, resulting in a low signal on brain MRI sequences. Several identified mutations correspond to expansions of repeated trinucleotides (CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCA8). A pentanucleotide repeat expansion (ATTCT) is associated with SCA10. Missense mutations have also been found recently. Anticipation is a main feature of SCAs, due to instability of expanded alleles. Anticipation may be particularly prominent in SCA7. It is estimated that extensive genetic testing leads to the identification of the causative gene in about 60-75 % of cases. Our knowledge of the molecular mechanisms of SCAs is rapidly growing, and the development of relevant animal models of SCAs is bringing hope for effective therapies in human.
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PMID:The wide spectrum of spinocerebellar ataxias (SCAs). 1589 52

Spino cerebellar ataxia (SCA) are a complex group of hereditary neurodegenerative disturbances of autosomal dominant pattern. They are largely characterized by the clinical presence of cerebellar ataxia related to ophtalmoplegia, dysarthria, pyramidal and extra-pyramidal signs and loss of deep sensitivity. SCA 7 belongs to the SCA group in which the disturbance is a result of the expansion of CAG triplet repetition located in the 3p12-p21 chromosome. The characteristic clinical feature of SCA7 is the loss of visual acuity and blindness. We present here three cases of ataxia, from the same family, with loss of visual acuity and other neurological disorders. The diagnosis was confirmed by a genetic analysis of the index case in whom the characteristic genetic abnormality of SCA7 was discovered. To our knowledge, this is the first case of SCA7 confirmed by genetic study in Argentina. Only two other reports on family cases were found in a review of the literature of Latin America up to January 2006. The purpose of our report is to draw attention to the diagnosis of this degenerative disease in patients with progressive cerebellar ataxia associated with loss of visual acuity symptoms, where a positive family history is found.
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PMID:[Spinocerebellar ataxia 7. Clinical and genetic investigation in an Argentine family]. 1759 99