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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a family showing dentatorubral-pallidoluysian atrophy. Three patients appeared through three successive generations and displayed a wide variety of clinical pictures. The male proband with onset in childhood showed progressive myoclonus epilepsy syndrome. The father experienced cerebellar ataxia, myoclonus, and mild dementia starting in middle age; the paternal grandmother had progressive symptoms of cerebellar ataxia, choreiform movements, and dementia, but neither myoclonus nor epilepsy in senescence. Neuropathologic examination of two patients, the proband and the paternal grandmother, revealed combined degeneration of the dentatorubral and pallidoluysian systems and obvious degeneration involving the striatum in the proband and the cerebellar cortex in the grandmother. The present study indicates that this disease can include many clinical and pathologic variants even in the same family.
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PMID:Hereditary dentatorubral-pallidoluysian atrophy: clinical and pathologic variants in a family. 338 24

Dentatorubral-pallidoluysian atrophy is an autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy, and dementia as well as a wide range of ages at onset. A specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 was recently identified as the pathogenic mutation for this disease. We investigated how the degree of expansion of the CAG repeat effects the clinical manifestations of dentatorubral-pallidoluysian atrophy. The size of the expanded alleles was well correlated with the age at onset (r = -0.696, p < 0.001). Patients with the progressive myoclonus epilepsy phenotype had larger expansions (62-79 repeats) and an earlier age at onset (onset before age 21). Furthermore, most of the patients with the progressive myoclonus epilepsy phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with the non-progressive myoclonus epilepsy phenotype showed smaller expansions (54-67 repeats) and a later age at onset (onset at or after age 21). Detailed analyses of clinical features demonstrated that ataxia, involuntary movement of either myoclonus or choreoathetosis, and intellectual decline are cardinal features of dentatorubral-pallidoluysian atrophy, with myoclonus and epilepsy being observed more frequently in patients with an earlier age at onset. Thus the wide variation in clinical manifestations of dentatorubral-pallidoluysian atrophy can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.
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PMID:Dentatorubral-pallidoluysian atrophy: clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat. 777 50

Anticipation refers to the progressively earlier onset and increase in disease severity in successive generations. We studied four families with hereditary dentatorubral-pallidoluysian atrophy (DRPLA), a neurodegenerative disease, and anticipation was present in the mode of inheritance. In subsequent generations DRPLA shows an earlier onset and more severe as well as additional symptoms. Older onset patients suffer from cerebellar ataxia with or without dementia, whereas younger onset patients present as progressive myoclonus epilepsy syndrome, which consists of mental retardation, dementia, and cerebellar ataxia as well as epilepsy and myoclonus. Anticipation with paternal transmission was significantly greater than with maternal transmission.
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PMID:Anticipation in hereditary dentatorubral-pallidoluysian atrophy. 800 97

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurologic disorder characterized by variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. By specifically searching published brain cDNA sequences for the presence of CAG repeats we identified unstable expansion of a CAG in a gene on chromosome 12 in all the 22 DRPLA patients examined. A good correlation between the size of the CAG repeat expansion and the ages of disease onset is found in this group. Patients with earlier onset tended to have a phenotype of progressive myoclonus epilepsy and larger expansions. We propose that the wide variety of clinical manifestations of DRPLA can now be explained by the variable unstable expansion of the CAG repeat.
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PMID:Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). 813 40

The clinical, genetic, and neuroradiologic characteristics of dentatorubral-pallidoluysian atrophy (DRPLA) are delineated in six patients from three generations of a Japanese family. The clinical characteristics of the disease varied, the age at onset depending on patients with juvenile-onset were characterized by myoclonus, epilepsy, and mental retardation whereas cerebellar ataxia, choreoathetosis, and dementia were typical of adult- and senile-onset patients. All affected individuals showed one expanded allele with the repeat number of CAG at the DRPLA locus, ranging from 58 to 82, and a normal allele, ranging from 10 to 21. The most severely affected patient, a case of maternal transmission and with the largest allele, became bedridden in a vegetative state by age 12. On the CT and MRI, varying degrees of brain atrophy were present in all patients. T2-weighted MRI in patients with senile-onset showed symmetric high-signal lesions in the cerebral white matter, globus pallidus, thalamus, midbrain, and pons. However, MRI in younger patients revealed no such lesions and CT failed to demonstrate lesions in the globus pallidus and brain stem. Thus, intrafamilial heterogeneity of DRPLA was also evident on MRI. High-signal lesions involving both, subcortical white matter and thalamus may be characteristics of senile-onset patients and may correlate with their dementia.
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PMID:Dentatorubral-pallidoluysian atrophy (DRPLA): clinical, genetic, and neuroradiologic studies in a family. 858 78

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

We report a family with autosomal recessive spastic paraplegia. Patient 1 was a 37-year-old woman and patient 2 was her 35-year-old sister. They showed spastic paraplegia with mild truncal ataxia and dysarthria but no dementia, epilepsy, myoclonus, or other involuntary movements. They were the products of a consanguineous marriage but the parents were neurologically normal. We analyzed the CAG repeats of the dentatorubral-pallidoluysian atrophy (DRPLA) gene in the family members. The patients were homozygous for an allele carrying an intermediate size of CAG repeats (41 or 40 repeats) in the DRPLA gene; the parents were heterozygous for an intermediate allele and a normal allele in this gene. Homozygosity for an intermediate allele in the DRPLA gene appears to have resulted in spastic paraplegia different from any DRPLA phenotype.
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PMID:Homozygosity for an allele carrying intermediate CAG repeats in the dentatorubral-pallidoluysian atrophy (DRPLA) gene results in spastic paraplegia. 910 5

We report a 60-year-old woman with progressive ataxia, myoclonus, choreoathetosis, and dementia. She was well until 27 years of the age when she noted an onset of gait disturbance and speech disturbance. She noted abnormal involuntary movements in her four limbs at 42 years of the age. Her symptoms had progressively become worse and she fell down frequently by her 52 years of the age. In addition, her family members noted gradual decline in her intelligence. She was admitted to our hospital in February of 1993 when she was 57-year-old. On admission, she showed dementia, scanning speech, ataxic gait, limb ataxia, action myoclonus, and choreic movements which involved her four limbs. Deep tendon reflexes were slightly exaggerated in the lower limbs; no Babinski sign was noted. Sensation was intact. Laboratory findings were unremarkable. Cerebral MRI revealed atrophy of the cerebellar cortex, superior cerebellar peduncle, brain stem, and the cerebral cortex; the third ventricle and the lateral ventricles were dilated; furthermore, T2-high signal lesions were seen in the cerebral white matter and in the pontine base. Her clinical course was one of the progressive deterioration of her ataxia, involuntary movements, and dementia. She expired on April 24, 1996 when she was 60-year-old. She was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had dentatorubral-pallidoluysian atrophy. A minor opinion was that she might have had myoclonus epilepsy with ragged-red fibers. Postmortem examination revealed atrophy, gliosis, and neuronal loss in the external segment of the globus pallidus, subthalamic nucleus, red nucleus, and in the dentate nucleus. In addition, the gracil and cuneiform nuclei showed neuronal loss and spheroid formation; the spinocerebellar tracts were retained. The substantia nigra and the locus coeruleus were intact. No ragged-red fibers were seen in the muscle biopsy specimen taken in February, 1993. The neuropathologic findings were consistent with the diagnosis of dentatorubral-pallidoluysian atrophy.
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PMID:[(Neurological CPC.55). A 60-year-old woman with progressive cerebellar ataxia, myoclonus, and dementia]. 923 57

Pathology and associated clinical symptoms of hereditary dentatorubral-pallidoluysian atrophy (H-DRPLA) which was established as a new inherited neurodegenerative disease in 1982 are described. Obligatory lesions in the central nervous system combine with degeneration of the dentatorubral and pallidoluysian pathway, and occasional degenerative lesions are found in the cerebral white matter, putamen, Goll's nucleus of the medulla oblongata, and lateral corticospinal and Goll's tract of the spinal cord. The main clinical symptoms are myoclonus, epilepsy, dementia or mental retardation, cerebellar ataxia and choreoathetosis. Furthermore, newly developing aspects in the pathology of H-DRPLA following the discovery of the gene locus of H-DRPLA in 1994 are briefly described.
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PMID:Hereditary dentatorubral-pallidoluysian atrophy. 1103 86

The genetic progressive myoclonus epilepsies (PMEs) are clinically characterized by the triad of stimulus sensitive myoclonus (segmental lightning like muscular jerks), epilepsy (grand mal and absences) and progressive neurologic deterioration (dementia, ataxia, and various neurologic signs depending on the cause). Etiologically heterogenous, PMEs are rare and mostly autosomal recessive disorders, with the exception of autosomal dominant dentatorubral-pallidoluysian atrophy and mitochondrial encephalomyopathy with ragged red fibers (MERRF). In the last five years, specific mutations have been defined in Lafora disease (gene for laforin or dual specificity phosphatase in 6q24), Unverricht-Lundborg disease (cystatin B in 21q22.3), Jansky-Bielschowsky ceroid lipofuscinoses (CLN2 gene for tripeptidyl peptidase 1 in 11q15), Finnish variant of late infantile ceroid lipofuscinoses (CLN5 gene in 13q21-32 encodes 407 amino acids with two transmembrane helices of unknown function), juvenile ceroid lipofuscinoses or Batten disease (CLN3 gene in 16p encodes 438 amino acid protein of unknown function), a subtype of Batten disease and infantile ceroid lipofuscinoses of the Haltia-Santavuori type (both are caused by mutations in palmitoyl-protein thiosterase gene at 1p32), dentadorubropallidoluysian atrophy (CAG repeats in a gene in 12p13.31) and the mitochondrial syndrome MERRF (tRNA Lys mutation in mitochondrial DNA). In this review, we cover mainly these rapid advances.
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PMID:Advances in the genetics of progressive myoclonus epilepsy. 1157 33


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