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Query: UMLS:C0008489 (chorea)
 2,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Huntington's Disease (HD) is a progressive degenerative disorder of the central nervous system inherited as an autosomal dominant trait. Clinically, the disorder is characterized by choreoathetosis (with age of onset typically in the late thirties or early forties) and neuropsychiatric disturbance. The striatum is particularly vulnerable to the degenerative disease process, with selective loss of medium spiny neurons and decreased levels of associated neurotransmitters, including substance P. GABA, met-enkephalin and dynorphin. Although the underlying pathophysiology is unknown, recent theories concerning pathogenesis have involved mitochondrial abnormalities and excitotoxin-mediated damage. The gene for HD has recently been discovered and characterized as an unstable CAG trinucleotide repeat sequence on the short arm of chromosome 4 (now known as IT15). The direct test now available for the HD gene has facilitated disease diagnosis, particularly for those with unclear family history or chorea of uncertain origin; presymptomatic testing is also available. Management of affected individuals is unsatisfactory as only symptomatic control is available. However, as the effect of the genetic abnormality may soon be known, specific treatment of the disorder may become available in the near future.
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PMID:Huntington's disease: recent advances in diagnosis and management. 775 74

The genetic mutation underlying Huntington's disease (HD) has been identified as an expansion and instability of a specific CAG repeat sequence in a gene (IT15) on chromosome 4. We have investigated the relation of the phenotype of HD to this molecular defect and assessed the feasibility of HD mutation analysis in diagnosis and prediction. Analysis of DNA from 449 HD patients (351 familial and 98 apparently isolated cases) revealed the mutation in more than 95% of patients from both groups. No molecular difference was found between patients presenting with psychiatric symptoms and those in whom chorea or other motor defects were the principal features; additionally, there was a wide range of age at onset for any specific repeat number, though the small group with juvenile onset and presenting with rigidity showed the largest expansions. The findings suggest that molecular analysis will be an accurate and specific diagnostic test for HD and valuable in presymptomatic detection in individuals at risk. However, such testing will require considerable caution to avoid serious difficulties; the well-established guidelines developed for the use of linked markers in relation to the prediction of HD should continue to be followed, though they will require reassessment in relation to use in diagnosis.
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PMID:Molecular analysis and clinical correlations of the Huntington's disease mutation. 790 91

Huntington disease (HD) is an autosomal-dominant disorder of mid-life onset characterized by chorea, dementia, and oculomotor disturbances. Anticipation is commonly seen in HD families, particularly when the disease is inherited through the father. The disorder is associated with an expanded (CAG)n repeat in the IT15 gene that is unstable and tends to increase in size during meiotic transmissions, particularly of paternal origin. We have detected an unusual form of HD on the island of Crete which has distinctly different characteristics. Data from eight families encompassing 48 HD patients, showed a median age at onset 15-20 years later than that for HD occurring worldwide. There is no juvenile cases and no anticipation. DNA analysis in 12 HD patients showed expansion of the (CAG)n repeat the size of which was identical among members of each family or varied by only one unit. The elongated DNA segment was passed stably or contracted during both paternal and maternal transmissions thus indicating that unique molecular mechanisms may be operational in this form of HD.
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PMID:Stability of the Huntington disease (CAG)n repeat in a late onset form occuring on the Island of Crete. 863 93

Huntington's disease (HD) is a progressive neurodegenerative disorder which is clinically characterized by chorea, cognitive decline, and emotional disturbance; it is inherited in an autosomal dominant manner. The HD gene maps to chromosome 4p16.3. Our linkage analysis demonstrated a significant genetic linkage between Japanese HD families and the flanking markers, D4S127, D4S43. The molecular basis of the disease is an expansion of CAG repeat in the huntingtin gene. We performed molecular analysis of the repeat in Japanese HD patients and normal controls. The size of the CAG repeat ranged from 37 to 95 repeats in affected subjects and from seven to 29 in normal controls. A significant correlation was found between the age of onset and the CAG expansion. The length of the expanded repeat is unstable in meiotic transmission and large increases occur in paternal transmission. At the same time the CCG repeat polymorphism adjacent to the CAG repeat was analysed and haplotypes of HD chromosomes were identified. Striking linkage disequilibrium was found between the CAG repeat expansion and an allele of (CCG)10 in Japanese HD chromosome. It is distinct from that described previously in western populations. Western HD chromosomes strongly associate with an allele of (CCG)7.
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PMID:[Molecular genetics of Huntington's disease]. 875 53

Benign familial chorea (BFC) is a rare neurological disease with an autosomal dominant transmission. The disorder is characterized by its early onset in childhood, a non-progressive course of choreatic movements and the absence of intellectual impairment. There is one study describing an expanded (CAG)n repeat in the gene IT15 (Huntington) on chromosome 4p (causative for Huntington's chorea) in a family reported to have BFC that was diagnosed on the basis of onset and non-progressive course. We failed to find an expansion of the (CAG)n repeats in an Austrian family having BFC. The three affected individuals of the family had 18-25 CAG repeats. These results indicate that the diagnostic criteria for BFC should include a normal result in the analysis of the (CAG)n repeat region of the Huntington gene.
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PMID:Normal CAG repeats in the Huntington gene in a family with benign familial chorea. 884 Mar 96

We describe the first Danish family with dentatorubral-pallidoluysian atrophy (DRPLA), containing 16 clinically affected individuals in five generations. Inheritance is autosomal dominant. The disorder was diagnosed as Huntington's disease (HD), but analysis of the IT15 gene for HD revealed normal alleles. The diagnosis of DRPLA was based on the finding of elongated CAG repeats in the B37 gene on chromosome 12 in affected individuals. The age at onset ranged from 13 to 60 years, with the most severe clinical picture being associated with onset in childhood. Clinical features included varying combinations of dementia, euphoria, visuomotor disturbances, speech problems, ataxia, tremor, epilepsy and involuntary movements presenting as chorea, athetosis, and dystonia. We discuss characteristics of DRPLA that may enable the differentiation from HD on a clinical basis. In conclusion, DRPLA should be considered and DNA analysis is recommended in patients manifesting varying combinations of extrapyramidal and cerebellar symptoms, especially when clinical features show pronounced intrafamilial variability, and dyscoordination, tremor, myoclonus, epilepsy, and euphoria are part of the syndrome.
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PMID:Dentatorubral-pallidoluysian atrophy. Clinical features of a five-generation Danish family. 886 94

Senile chorea (SC) is characterized by the presence of late onset, generalized chorea with no family history and no dementia. It is unclear whether it is a distinct clinical entity or represents late onset Huntington's disease (HD) with an undetected family history. In order to clarify this issue, we carried out a prospective, multicenter study of suspected cases of SC. Since 1994 we identified six cases that met clinical criteria for SC. Their study included routine lab tests, cerebral MRI, neuropsychological assessment, and lastly gene IT15 analysis. An abnormal expansion of the (CAG)n repeat was found in three patients. Although there were no criteria for dementia, most neuropsychological tests revealed mild to moderate deficits, particularly in visuospatial and prefrontal tasks, m all six patients, those that were finally diagnosed as having late onset "sporadic" HD, but also in patients that finally had SC. This study provides further evidence on the existence of SC; however, the distinction from late onset "sporadic" HD seems not to be possible on clinical grounds unless a genetic study is carried out. Some cases of suspected "SC" have late onset "sporadic" HD.
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PMID:Senile chorea: a multicenter prospective study. 908 88

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder that clinically overlaps with Huntington's disease (HD) and manifests combinations of chorea, myoclonus, seizures, ataxia, and dementia. DRPLA is caused by a CAG triplet repeat (CTG-B37) expansion coding for polyglutamine on chromosome 12 and exhibits the genetic phenomenon of anticipation. This neurodegenerative disease has only rarely been reported in non-Japanese pedigrees, and there are only a few neuropathological studies in genetically confirmed patients. We report 10 cases of DRPLA from two North American and two British pedigrees in which CTG-B37 expansions have been demonstrated within each kindred (54-83 repeats), individually in 8 of the 10 cases, and describe the neuropathological findings in 4 cases. Members of DRPLA kindreds have a wide range of clinical phenotypes and markedly variable ages at onset. The neuropathological spectrum is centered around the cerebellifugal and pallidofugal systems, but neurodegenerative changes can be found in many nuclei, tracts, and systems. Evidence of CTG-B37 triplet repeat expansion should be sought in HD-like cases that are negative for expanded triplet repeats within the HD IT15 gene or in autopsy cases with degeneration of the dentatorubral or pallidoluysian systems.
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PMID:Dentatorubral and pallidoluysian atrophy (DRPLA). Clinical and neuropathological findings in genetically confirmed North American and European pedigrees. 975 63

The diagnosis of Huntington's disease (HD) can be confirmed by detecting the expanded CAG repeat in the IT15 gene. Besides chorea, patients with HD may present with a variety of bizarre involuntary movements, resulting in confusion in making the diagnosis. Under such conditions, genetic analysis is the final confirmatory test. To determine if any patient with involuntary movements of undetermined etiology might be related to HD, we did genetic analysis on 22 patients and identified three with expanded CAG repeat. We could not obtain family history of HD in these patients due to adoption, early death of parents, or a vague history. All three patients were among the group with generalized chorea, but one had additional marked dystonic posturing. Together with four clinically recognizable HD patients, the relative frequency of HD among the 103 patients with choreiform movements in this hospital is 6.8%.
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PMID:Genetic screening for Huntington's disease in Chinese patients with involuntary movements. 949 Dec 97

Huntington disease (HD) is an adult-onset, autosomal dominant inherited human neurodegenerative disorder characterized by hyperkinetic involuntary movements, including motor restlessness and chorea, slowing of voluntary movements and cognitive impairment. Selective regional neuron loss and gliosis in striatum, cerebral cortex, thalamus, subthalamus and hippocampus are well recognized as neuropathological correlates for the clinical manifestations of HD. The underlying genetic mutation is the expansion of CAG trinucleotide repeats (coding for polyglutamines) to 36-121 copies in exon 1 of the HD gene. The HD mRNA and protein product (huntingtin) show widespread distribution, and thus much remains to be understood about the selective and progressive neurodegeneration in HD. To create an experimental animal model for HD, transgenic mice were generated showing widespread expression of full-length human HD cDNA with either 16, 48 or 89 CAG repeats. Only mice with 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction with neuron loss and gliosis in striatum, cerebral cortex, thalamus and hippocampus. These animals represent clinically relevant models for HD pathogenesis, and may provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.
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PMID:Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. 977 16


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