Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report the clinical and laboratorial findings of 5 affected members (all males) of a family with Machado-Joseph disease. The mode a inheritance was autosomal dominant. The mean onset age was 38 years (range 30-50 years). The clinical picture was pleomorphic and included cerebellar ataxia, external ophthalmoplegia with bulging eyes, extrapyramidal/pyramidal syndromes, amyotrophy with fasciculations and peripheral neuropathy, in variable degrees of severity. In one patient parkinsonian rigidity was greatly improved with the use of trihexaphenidyl and L-dopa. CT scan examinations disclosed a variable degree of cerebellar atrophy, with mild cerebral atrophy in one patient. Brainstem evoked potentials were normal in two patients. EMG showed denervation in three patients. Muscle biopsy (gastrocnemium) with histochemical studies revealed chronic muscle denervation in four cases. Sural nerve biopsy with conventional pathological study was normal in four cases. This family was living in Florianopolis, Santa Catarina, where there is a great number of Portuguese descendants from the Azores Islands. The worldwide presence of the disease seems to result from the genic diffusion of the disease with the Portuguese emigration during the Great Navigations Era and with some later emigratory settlement.
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PMID:[Machado-Joseph disease: description of 5 members of a family]. 181 Feb 35

One male and two female cases in a family of Machado-Joseph disease were reported. Two cases showed typical symptoms that are characterized by bulging eyes, ophthalmoplegia, dystonia, ataxia, spasticity of extremities and amyotrophy, and were consistent with Type II (Rosenberg et al). But another one lacked diversity of the symptoms, showing mainly progressive cerebellar ataxia for over 10 years. We pointed out the existence of a new type of MJD case exhibiting only progressive cerebellar ataxia over a long period. A female patient had dyspnea and insomnia after 20 years in her clinical course, and central sleep apnea was revealed by respiratory monitor. But, the apnea and irregular respiration appeared in both awake and sleep stages. We described the importance of attention to the apnea as a new complication of Machado-Joseph disease.
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PMID:[A family of Machado-Joseph disease with a patient having frequent apnea in all day]. 191 27

The clinical and pathological findings in a 58-year-old Japanese man suffering from type III Machado-Joseph disease are reported. The patient became affected at the age of 50 years and presented cerebellar ataxia, progressive external ophthalmoplegia and muscular atrophy, although extrapyramidal signs were never detected throughout the whole course of his disease. His mother, sister and son presented progressive ataxia in the third or fourth decade. The mode of inheritance is considered to be autosomal dominant. Pathological examination revealed severe involvement of the dentato-rubral, ponto-cerebellar and subthalamopallidal systems, spinocerebellar tracts and Clarke's column, cranial motor nuclei including the oculomotor systems and anterior horn cells. The involvement of the substantia nigra was relatively mild, and the nerve cells in the inferior olivary nucleus were well preserved. The distal portion of peripheral nerves was severely damaged. Although the striking feature of Machado-Joseph disease is a considerable variability in the individual clinical expression, there have not been many autopsied cases of this disease and efforts to clarify the clinico-pathological correlation in each phenotype have scarcely been made. Relatively mild changes in the substantia nigra and severe involvement of the peripheral nervous system, as in our case, may be the pathological hallmarks of the type III disorder.
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PMID:Type III Machado-Joseph disease in a Japanese family: a clinicopathological study with special reference to the peripheral nervous system. 274 50

The clinical observations in five patients, of a family of catalan origin (NE of Spain), affected with Machado-Joseph disease are reported. The pedigree showed the presence of 22 members affected (15 men, 7 women) over six generations. The symptoms and signs were variable among the patients and also variable in a same patient during the course of the disease. However, the main neurological alterations were ataxia, akinesia, distal amyotrophy, progressive external ophthalmoplegia, facial and lingual fasciculations and bulging eyes. The neuropathological examination performed in one patient disclosed degeneration of the posterior and spinocerebellar tracts in the spinal cord, marked nerve cell loss in Clarke's column and anterior horns and axonal degeneration of the peripheral nerves, in addition to nerve cell loss in the nuclei of the III, IV and VII cranial nerves and neuronal depletion in the substantia nigra. No other structures, including the striate complex and dentate nucleus, were significantly affected.
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PMID:[Machado-Joseph disease in a family of Spanish origin]. 347 47

The clinical and pathological findings in a boy suffering from Machado-Joseph disease are described. The patient was the son of two affected parents and signs first appeared at the age of 8 years. A younger brother also became affected at the age of 7. The patient presented all the characteristic features of the disease which consist of progressive cerebellar ataxia, pyramidal signs, progressive external ophthalmoplegia with variable degrees of extrapyramidal and peripheral signs. He died at the age of 15, after an unusually short duration of the disease. Pathological examination showed degeneration and mild gliosis of the substantia nigra, dentate, pontine and cranial nerve nuclei, anterior horns and Clarke's columns. Additional findings, not previously described were the involvement of sensory ganglia, intermediolateral columns and gracile and cuneate nuclei. It is suggested that the present case is homozygous for the gene of Machado-Joseph disease. The pattern of distribution of the pathological lesions and the sparing of some anatomical structures confirm our view that Machado-Joseph disease should be considered a distinct clinico-pathological entity within the group of the autosomal dominant ataxias.
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PMID:The pathology of Machado-Joseph disease. Report of a possible homozygous case. 713 16

A Portuguese family of non-Azorean origin is described as affected by an autosomal dominant inherited ataxia resembling Machado-Joseph disease. Clinical criteria for diagnosis are proposed, based on a complex clinical picture extending from extrapyramidal signs to peripheral amyotrophy associated with secondary, but more specific, minor features such as progressive external ophthalmoplegia, dystonia, intention fasciculation-like movements of facial and lingual muscles, and bulging eyes. Machado-Joseph disease may be more widespread than previously believed.
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PMID:Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorena Portuguese family. 718 34

Patients with spinocerebellar ataxia 3 (SCA3) and Machado-Joseph disease (MJD) carry an expanded CAG repeat in the MJD1 gene. One hundred twenty families of different geographic origin with autosomal dominant cerebellar ataxia (ADCA) type I were tested. Thirty-four families (126 patients) carried an expanded CAG repeat. The expanded and the normal allele did not overlap and the repeat was unstable during transmission, with variation in the size of the CAG length ranging from -8 to +5 and a mean expansion of 0.86 repeats without differences according to the parental sex. There was a combined effect of the number of CAG repeats of the expanded and normal allele on the age at onset, which accounted for 70% of its variability. The length of the CAG repeat influenced the frequency of clinical signs associated with cerebellar ataxia, such as abnormal tendon reflexes or decreased vibration sense, whereas the interindividual variation of supranuclear ophthalmoplegia, sphincter and swallowing difficulties, and amyotrophy was mostly determined by different disease durations. We compared the clinical profile of 91 SCA3/MJD patients with 51 SCA1 and 32 SCA2 patients. There were striking differences between the SCA3/MJD and SCA2 but not with SCA1 groups of patients. Despite their clinical similarities, distinct neuropathological features were observed in 2 SCA3/MJD and 2 SCA1 patients.
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PMID:Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. 861 27

Trinucleotide repeat expansion in the Machado-Joseph disease (MJD) gene has been found in 26 patients from 20 unrelated Japanese families. Expanded alleles had 68 to 84 repeats, whereas normal alleles had 14 to 37 repeats. The age of onset was inversely correlated with the repeat length. To evaluate in detail the relationship between the repeat length and clinical features, we subdivided the 26 patients into three groups on the basis of the repeat length (group 1, 78 repeats or more; group 2, 74 to 77 repeats; group 3, 73 repeats or less). Group 1 and group 2 had common features of spasticity, hyperreflexia, Babinski sign, bulging eyes, facial myokymia and extrapyramidal signs as well as cerebellar ataxia and ophthalmoplegia. It should be noted that group 1 showed more prominent pyramidal and extrapyramidal signs than group 2. In contrast, group 3 showed hypotonia, hyporeflexia and sensory disturbance in addition to cerebellar ataxia and ophthalmoplegia. These findings suggest that the repeat length plays an important role in phenotypic variation. DNA analysis for the MJD mutation was clearly useful for making an accurate diagnosis in patients without bulging eyes, facial myokymia, dystonia or marked spasticity.
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PMID:The relationship between trinucleotide repeat length and phenotypic variation in Machado-Joseph disease. 883 72

We studied 83 patients from 36 Italian families with autosomal dominant cerebellar ataxia type I. Mean onset age +/- SD was 34.2 +/- 12.8 years with a mean anticipation of 12.8 +/- 15.1 in 52 parent-offspring pairs. Onset age anticipation occurred predominantly through paternal transmission. Mean age at death was at 56.5 +/- 15.5 years. The most common associated features were supranuclear ophthalmoplegia, corticospinal signs, peripheral neuropathy and cognitive impairment. Cerebellar atrophy was constant at MRI and usually associated with shrinkage of the pons and degeneration of the pontine transverse fibres. Direct mutation analysis in 29 families showed two families with SCA1 and none with Machado-Joseph/SCA3 mutation. We performed linkage analysis in the ten largest families. Two of them showed linkage to SCA2 locus and none to SCA4 and SCA5 loci. SCA2 patients showed higher occurrence of peripheral neuropathy and slow saccades, rarer corticospinal signs and a milder course of the disease in comparison with SCA1 patients.
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PMID:Autosomal dominant cerebellar ataxia type I. Clinical and molecular study in 36 Italian families including a comparison between SCA1 and SCA2 phenotypes. 890 34

Machado-Joseph disease (MJD) is an autosomal dominantly inherited neurodegenerative disorder characterized by varying age of onset and pronounced phenotypic heterogeneity. The clinical core features include gait ataxia, external ophthalmoplegia, nystagmus, and bulging eyes. Recently, Kawagushi et al. (1994) cloned the MJD1 gene on chromosome 14 and MJD turned out to be the fifth neurodegenerative disease caused by an unstable CAG repeat expansion. We have studied two large Danish families and one Norwegian family with MJD. Three features not previously associated with MJD are reported: dementia, generalized muscle and joint pain, and in one case neuropathological examination revealed atrophy of the inferior olives. We found a significant inverse correlation between age of onset and the length of the CAG repeat expansion, and anticipation is described through four succeeding generations. Instability of the CAG repeat expansion was most pronounced at paternal transmission.
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PMID:Machado-Joseph disease in three Scandinavian families. 958 50


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