Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From the linkage study of D6S89, we previously reported that hereditary OPCA in Japan is genetically heterogenous. Two pedigrees, P2 and P35, reported in this report, were not linked to D6S89. In order to examine possible correlation between OPCA genotypes and disease phenotypes, we studied clinically eight cases in these two pedigrees. One autopsied case in pedigree P2 was proven to have marked neuronal degeneration in the inferior olivary nuclei, pontine nuclei, cerebellar cortex, and substantia nigra. Dentate nucleus and oculomotor nuclei were free from neuronal degeneration. Clinical features of those 8 patients were fairly uniform, characterized by cerebellar ataxia, hypoactive DTR, and slow eye movement. Parkinsonism or choreiform movements were observed in one patient, respectively. Pupillary dilatation, twitching of face and tongue, limb amyotrophy were observed in patients of advanced stages. However, these signs were not dominating nor common throughout clinical course. None of our cases showed hyperactive DTR, limb spasticity, or external ophthalmoparesis. On the other hand, these latter signs were popular in SCA1 so far as reviewing the literature. The present study showed that there was possible correlation between genotypes and phenotypes in hereditary OPCA.
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PMID:[Clinical study of gene locus heterogeneity in hereditary olivopontocerebellar atrophy (OPCA)--report of 2 pedigrees affected with non SCA1 type OPCA]. 181 83

Affected members of 63 families with a variety of autosomal dominant late onset cerebellar ataxias (ADCA), and 29 patients with similar phenotypes but no affected relatives, were investigated for the trinucleotide (CAG) repeat expansion described in Japanese families with Machado-Joseph disease (MJD). This disorder had previously been shown to map to the region of chromosome 14 which also contains a locus causing ADCA in French families, spinocerebellar ataxia 3 (SCA3). The MJD/SCA3 mutation was identified in nine families with ADCA type I, and a further family in which affected members had parkinsonism, peripheral neuropathy, dystonia, and spasticity, but little evidence of cerebellar disease. Only one of the 10 families was British (the Drew family of Walworth); the others originated from India, Jamaica, Ghana, Brazil and France. There was no single clinical feature which distinguished patients with the MJD/SCA3 mutation from those with the CAG expansion on chromosome 6 (SCA1) or ADCA type I families with no known mutation. The CAG repeat length ranged from 13-41 copies on normal chromosomes and 62-80 copies on affected chromosomes. There was a significant inverse correlation between age of onset of symptoms and repeat length, but no significant effect of parental sex on repeat length or age of onset in offspring. DNA analysis for the MJD/SCA3 mutation is useful for diagnosis in patients with familial ataxic or extrapyramidal syndromes, and will aid genetic counselling in these disorders.
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PMID:Detection of the Machado-Joseph disease/spinocerebellar ataxia three trinucleotide repeat expansion in families with autosomal dominant motor disorders, including the Drew family of Walworth. 749 71

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

There are currently some types of autosomal dominant cerebellar ataxias such as Machado-Joseph disease (MJD), spinocerebellar ataxia types 1-5 (SCA1-5), or hereditary dentatorubropallidoluysian atrophy. It is very important for these ataxias to be clinically differentiated, but that is sometimes difficult. In particular, the differential diagnosis between MJD and SCA1 is thought to be the most difficult. Recently, both MJD and SCA1 have been proven to be related to expansions of CAG trinucleotide in their causative genes. In this study, 20 cases of MJD in 13 unrelated Japanese families were genetically and clinically examined in comparison with 20 cases of age at onset- and duration-matched Japanese SCA1. The CAG repeat number of expanded MJD and SCA1 alleles was 72.2 +/- 3.1 (mean +/- SD, n = 20) and 47.3 +/- 4.4 (n = 20), respectively, and each repeat size was inversely correlated with age at onset in both MJD and SCA1. The repeat number in leukocytes increased from parents to children with acceleration of age at onset (anticipation) in MJD. In MJD, the number of CAG repeats in the expanded allele was lower in sperm than that of leukocytes, but was more in SCA1. However, the number of peaks in the expanded allele was greater in sperm than in leukocytes in both MJD and SCA1 (increased mosaicism level). MJD was clinically characterized by a relatively higher frequency of ocular signs such as eyelid retraction, bulging eyes, ophthalmoparesis, and nystagmus, spasticity in lower limbs, and sensory and urinary disturbances in contrast to the SCA1 patients except for slow eye movement. These results indicate that the expanded CAG repeat and clinical features are correlated in both MJD and SCA1, and MJD can be differentiated from SCA1 by clinical characteristics mentioned above as well as DNA analysis.
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PMID:Analysis of CAG trinucleotide expansion associated with Machado-Joseph disease. 881 56

SCA1 is a dominant spinocerebellar ataxia (SCA) and a multi-systemic syndrome caused by abnormal expansion of unstable CAG repeat in a novel gene located on chromosome 6p22-p23. We clinically studied 35 Japanese SCA1 patients who were assumed to have come from a common origin. The age at onset ranged from 15-63 years, and significantly correlated with CAG repeat units of mutant alleles. Ataxia was the initial symptom, and the majority of patients had a similar history of signs and symptoms. Nystagmus was at first minimal, later attenuated, and a slow saccade followed. Limb tendon reflexes were mostly hyperactive and depressed with the development of diffuse amyotrophy. The cardinal feature was ataxia-hyperreflexia-late slow saccade syndrome with terminal amyotrophy. Although the phenotype of SCA1 overlaps with those of other dominant SCAs, some facets of the neurological events differ from either SCA2 with ataxia-hyporeflexia-slow saccade syndrome, or early-onset Machado-Joseph disease with dystonia-bradykinesia-spasticity syndrome.
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PMID:Clinical features and natural history of spinocerebellar ataxia type 1. 882 76

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

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

The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1-3, 6-8, 12, 17; dentate-rubro-pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia.
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PMID:Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients. 1670 60