Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family is described in which five males have late-onset facial weakness, dysarthria, dysphagia, and slowly progressive proximal weakness. Electrodiagnostic studies and muscle biopsy were compatible with spinal muscular atrophy. This family appears quite similar to several previously reported families with late-onset X-linked recessive spinal and bulbar muscular atrophy. Because of the relative homogeneity of this particular phenotype of spinal muscular atrophy, a single metabolic derangement was sought. Three obligate carriers were studied, and no abnormality was detected. A further family with this condition is briefly discussed.
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PMID:Late-onset X-linked recessive spinal and bulbar muscular atrophy. 57 30

Kennedy's disease (spinal and bulbar muscular atrophy) is an X-linked form of motor neuron disease that affects adult men. The syndrome is characterized by progressive atrophy of the limb muscles, pelvic and shoulder girdles and dysphagia and dysarthria, and is caused by the degeneration of spinal and bulbar motor neurons. Kennedy's disease is caused by a trinucleotide repeat expansion of a CAG repeat in exon A of the androgen receptor gene, and is one of a group of neurological diseases caused by trinucleotide repeat expansions in different genes. The mutation in Kennedy's disease involves an increased number of glutamine residues in the amino-terminal domain of the receptor. Point mutations and deletions in the androgen receptor gene cause androgen insensitivity syndrome, however subjects with Kennedy's disease have normal virilization, although progressive gynaecomastia, testicular atrophy and infertility may occur. Androgen receptors are expressed widely in the normal brain, and in the anterior horn cells of the spinal cord; however, their role in neuronal tissue is not known, nor is it known how the androgen receptor gene mutation causes neuronal degeneration. Kennedy's disease is likely to be a 'gain of function' abnormality, so that the presence of the receptor with an increased number of glutamines is toxic to motor neurons. It is possible that the mutation alters interaction of the receptor with other neuronal transcription factors, or neuronotoxicity may occur because of a non-specific effect caused by the presence of a protein with a large homoglutamine domain. Studies of patients with Kennedy's disease have shown that expression of androgen receptor mRNA and protein in spinal cord may be decreased, as can be the affinity of the mutant receptor for androgen. In vitro studies have shown impaired transcription activation ability of the mutant androgen receptor. The age at onset of Kennedy's disease may correlate with the size of the CAG repeat, however there is a large degree of variability of age at onset between subjects with the same number of repeats. Further study of the effect of the Kennedy's disease mutation on androgen receptor function in motor neurons will allow us to increase our understanding of the pathogenesis of this disease.
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PMID:Spinal and bulbar muscular atrophy: androgen receptor dysfunction caused by a trinucleotide repeat expansion. 886 71

The X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is a rare X-linked, recessive, lower motor neuron disease, characterized by weakness, atrophy, and fasciculations of the appendicular and bulbar muscle. The disease is caused by an expansion of the CAG repetition in the androgen receptor gene. Patients with Kennedy's disease have more than 39 CAG repetitions. We report a case of 57-year-old man, resident of Monte Dourado (PA, Brazil) who complained of brachiocrural paresis evolving for 3 years along with fasciculations and tremors of extremities. In addition, he also developed dysarthria, dysphagia, and sexual dysfunction. The patient clinical picture included gait impairment, global hyporeflexia, proximal muscle atrophy of upper limbs, deviation of the uvula to right during phonation and tongue atrophy with fasciculations. The patient reported that about 30 years ago he had undergone gynecomastia surgery. His electroneuromyography suggested spinal muscular atrophy, and nuclear magnetic resonance imaging showed tapering of the cervical and thoracic spinal cord. Patient's creatine kinase level was elevated. In view of the findings, an exam was requested to investigate Kennedy's disease. The exam identified 46 CAG repetitions in the androgen receptor gene, which confirmed the diagnostic suspicion. This was the first case of Kennedy's disease diagnosed and described in the Brazilian Amazon. To our knowledge only other four papers were published on this disease in Brazilian patients. A brief review is also provided on etiopathogenic, clinical and diagnostic aspects.
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PMID:X-linked spinal and bulbar muscular atrophy (Kennedy's disease): the first case described in the Brazilian Amazon. 2989 93