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)

Wolfram syndrome was originally described as a combination of familial juvenile-onset diabetes mellitus and optic atrophy. Other neurological features subsequently emerged, and "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) became a commonly accepted acronym. Here, we describe 4 further cases from 2 families, in whom there occurred previously unrecognized neurological features, central apnea and neurogenic upper airway collapse, together precipitating primary respiratory failure (fatal in 1 case), startle myoclonus (in 2 unrelated cases), axial rigidity, and Parinaud's syndrome. Magnetic resonance images revealed striking brainstem atrophy affecting, in particular, the pons and midbrain. The mitochondrial DNA from 3 cases (and relatives) showed no evidence of any of the previously reported abnormalities. These neurological and neuroradiological features, in conjunction with (1) analyses showing the neurodegenerative origin of optic atrophy, deafness, diabetes insipidus, and incontinence, (2) other previously reported neurological complications (including anosmia, ataxia, epilepsy, and neuropsychiatric and cognitive abnormalities), and (3) the very small number of published postmortem studies, indicate that Wolfram syndrome should be reemphasized as a unique hereditary neurodegenerative disorder with prominent optic atrophy and diabetes mellitus.
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PMID:Wolfram syndrome: hereditary diabetes mellitus with brainstem and optic atrophy. 860 54

Paraneoplastic encephalomyelitis developed as the presenting feature of small-cell lung carcinoma in 3 patients. Two patients with paraneoplastic encephalomyelitis manifested predominantly as subacute sensory neuronopathy did not improve after prednisone treatment and chemotherapy. The third patient had severe axial and limb rigidity and myoclonus, which partially improved after chemotherapy and treatment with intravenous immunoglobulin and prednisone. Serum from each patient immunocytochemically stained the neuropil and to a lesser degree the neuronal cytoplasm in human cerebral and cerebellar cortex. On immunoblots of human neuronal extracts, each patient's serum contained high-titer IgG antibodies reacting with a protein band of apparent molecular mass 125 kd. This autoantibody pattern is indistinguishable from antibodies recently identified in several women with breast carcinoma and stiff-man syndrome. Screening of a human brain complementary DNA expression library with patient serum yielded clones whose sequence is identical to that of the synaptic vesicle-related protein amphiphysin. Reverse transcriptase-polymerase chain reaction demonstrated expression of amphiphysin in 8 of 10 small-cell lung carcinomas and in 5 of 14 breast carcinomas. These observations highlight the clinical and serological heterogeneity of paraneoplastic central nervous system disorders: Patients with a given clinical syndrome may have different antineuronal antibodies, and patients with a given autoantibody specificity have differing clinical presentations.
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PMID:Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. 861 52

A rare point mutation at nucleotide position 8356 in the transfer RNA gene in mitochondrial DNA was found in a Japanese family. Our proband had migraine and dementia associated with lactic acidosis in addition to myoclonic epilepsy with ataxia and ragged-red fibres in a muscle biopsy specimen consistent with the clinical characteristics of myoclonic epilepsy with ragged-red fibres (MERRF). His mother, who had the same point mutation, also had migraine but without myoclonus or ataxia. His aunt, who had the same point mutation and migraine, developed diabetes mellitus, encephalomyopathy and several stroke-like episodes associated with lactic acidosis (MELAS). This is the third family with the rare mutation seen in American and Italian families. The mutation may not be specific to Caucasians, and is probably closely related to the MERRF/MELAS overlap syndrome.
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PMID:The T-C(8356) mitochondrial DNA mutation in a Japanese family. 880 15

We report a 6-month-old girl with episodic hyperventilation, myoclonus, disturbed consciousness, and lactic acidosis. Brain sonogram revealed progressive ventriculomegaly, and MRI showed symmetric low densities over the putamen bilaterally with diffuse cortical cystic lesions. Ragged-red fibers were noted in the muscle biopsy. Molecular analysis revealed a heteroplasmic T-->G mutation at nucleotide position (np) 8993 of mitochondrial DNA (mtDNA). The proportion of the mutant mtDNA in the muscle of the proband was estimated to be 86%. Her mother and maternal uncle also harbored the same mutant mtDNA (54 and 48% in their leukocytes, respectively). One of her sisters carried 64% mutant mtDNA in her leukocytes, but another sister did not. These results suggest that this mutant mtDNA is transmitted through the maternal lineage in this family in a randomly segregated manner. To our knowledge, this is the first report of a Chinese patient with Leigh syndrome associated with the T-->G substitution at np 8993 of mtDNA.
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PMID:Leigh syndrome associated with mitochondrial DNA 8993 T-->G mutation and ragged-red fibers. 885 7

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

Mediterranean myoclonus is a progressive myoclonus epilepsy with autosomal recessive inheritance. Another form has been described in Finland, the so-called Baltic myoclonus. Mediterranean myoclonus and Baltic myoclonus are also known as Unverricht-Lundborg disease. Linkage analyses have shown that the genes for both these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting that they are caused by mutations at the same locus (EPM1). Recently, two heterozygous mutations were found in the cystatin B gene in patients with Unverricht-Lundborg disease. We report recombinational and linkage disequilibrium mapping of EPM1, and cystatin B gene sequencing, in 14 consanguineous pedigrees with Mediterranean myoclonus. Linkage to 21q22.3 DNA markers was observed in all these families. Haplotype analysis suggests that a common mutation segregates within these pedigrees, and that this mutation is different from the common one responsible for the Finnish form of Unverricht-Lundborg disease. No mutation was found in the exons or splice junctions of the cystatin B gene in the 14 pedigrees.
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PMID:Allelic heterogeneity of Mediterranean myoclonus and the cystatin B gene. 915 33

Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. One hundred and eighty four index patients with autosomal dominant cerebellar ataxia type I were screened for this mutation. We found expansion in 109 patients from 30 families of different geographical origins (15%) and in two isolated cases with no known family histories (2%). The SCA2 chromosomes contained from 34 to 57 repeats and consisted of a pure stretch of CAG, whereas all tested normal chromosomes (14-31 repeats), except one with 14 repeats, were interrupted by 1-3 repeats of CAA. As in other diseases caused by unstable mutations, a strong negative correlation was observed between the age at onset and the size of the CAG repeat (r = -0.81). The frequency of several clinical signs such as myoclonus, dystonia and myokymia increased with the number of CAG repeats whereas the frequency of others was related to disease duration. The CAG repeat was highly unstable during transmission with variations ranging from -8 to +12, and a mean increase of +2.2, but there was no significant difference according to the parental sex. This instability was confirmed by the high degree of gonadal mosaicism observed in sperm DNA of one patient.
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PMID:Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families. 915 45

We report two brothers with familial Creutzfeldt Jakob disease (CJD) having a heterozygous point mutation at codon 200 of the prion protein gene (Glu-->Lys): CJD200. The brothers were born in Kitakoma-gun, Yamanashi Prefecture. Patient 1, a 62-year-old man, developed CJD in 1995 and died nine months later. Patient 2, his brother, developed CJD200 at the age of 58 in 1982 and died 13 months later. They both exhibited rapidly progressive dementia with myoclonus and periodic synchronous discharges on electroencephalograms and became bedridden with three or four months. DNA analysis of peripheral blood cells of patient I showed a point mutation in the prion protein gene at codon 200: GAG-->AAG (Glu-->Lys). Five families with CJD200, 11 patients, have been reported in Japan to date, and nine of the patients from four families were born in Yamanashi Prefecture and vicinity. Our patients were born in the same area. We suspect that there is a cluster of CJD200 in Yamanashi Prefecture and vicinity. In Europe and America the phenotype of CJD200 has been reported to be heterogeneous, whereas the clinical features in Japanese cases are fairly homogeneous. We suspect that these patients have a common ancestor with a codon 200 mutation, and that that explains why the phenotypes are homogeneous.
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PMID:[Familial Creutzfeldt-Jakob disease with the heterozygous point mutation at codon 200 of the prion protein gene (Glu-->Lys)--report of CJD200 brothers of Yamanashi Prefecture origin]. 916 60

Whipple's disease of the central nervous system (CNS) may be associated with normal intestinal histology as a result of minimal or patchy involvement. The diagnosis is difficult and is frequently made post mortem. We studied 6 patients with clinically suspected CNS Whipple's disease; 2 had oculomasticatury myorhythmia (OMM) fitting criteria for a diagnosis of definite CNS Whipple's disease. One of the 2 had duodenal histology highly suggestive of Whipple's disease the other 5 patients had normal duodenal histology. DNA was extracted from paraffin-embedded duodenal tissues in all patients and frozen pontine tissue in 1. Two primer pairs (W3F-W4R, W3F-W2R) were used in separate polymerase chain reactions (PCRs) to amplify fragments of Tropberyma whippelii 16S rDNA from these tissue samples. PCR amplicons were detected only in the duodenal tissues from the 2 patients with OMM. The sequences of these amplicons were identical to the corresponding region of the previously published Tropheryma whippelii 16S rDNA sequence. PCR-based assays of intestinal or brain tissue may be of value for confirming, and possibly refuting, a clinical diagnosis of CNS Whipple's disease in a patient with any combination of dementia, supranuclear gaze palsy, hypothalamic manifestations, myoclonus, seizures, ataxia, or OMM, especially when tissue histology is unrevealing.
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PMID:Polymerase chain reaction-based detection of Tropheryma whippelii in central nervous system Whipple's disease. 922 95

Primary defects of mitochondrial DNA leading to respiratory chain dysfunction have been described in association with dystonia, chorea and parkinsonism. Myoclonus remains the commonest movement disorder associated with such defects. The genetic basis of Leigh's syndrome, which is frequently associated with movement disorders, may be mitochondrial or nuclear. Respiratory chain dysfunction has been identified in Huntington's disease in addition to Parkinson's disease, but the cause and relationship of this dysfunction to the pathogenesis of these common disorders is not yet determined.
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PMID:Movement disorders and mitochondrial dysfunction. 926 61


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