Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endemic cretinism has been classified into neurological and myxedematous types. Profound mental deficiency, deaf-mutism and cerebral diplegia are predominantly found in the former. The latter have been described as less mentally retarded but with severe growth retardation and myxedematous features. The pathogenesis of different clinical types of endemic cretinism is still unclear. Recently, a unifying hypothesis suggested that iodine deficiency, severe enough to cause maternal and fetal hypothyroxinemia, results in neurological defects in all cretins. We conducted the present study in northern Thailand to determine the validity of this hypothesis in another geographical area. The study consisted of a multidisciplinary survey on 112 endemic cretins aged 2-66 years in Nan. They were categorized clinically into three types of endemic cretins, neurological (n = 57), myxedematous (n = 19) and mixed form (n = 36). The subjects were generally short and the majority had severe mental retardation (mean intellectual quotient (I.Q.) 30.8 +/- 8.8), psychomotor defect and profound sensorineural hearing loss. The I.Q. score and proportion of cretins with sensorineural hearing loss and psychomotor defect were similar among the three types of cretins. The most frequent neurological abnormalities were spasticity, hyper-reflexia, the presence of primitive reflexes and gait disturbance. These abnormalities were distributed equally among the three types of endemic cretins. Delayed skeletal maturation and abnormal epiphysis were also present in all types of cretins. However, myxedematous cretins were shorter (P < 0.01), having more myxedematous features (P < 0.05 to P < 0.001) and less sexual maturation (P < 0.05). Thyroid volume was lower in cretins with hypothyroidism (P < 0.01). In conclusion, our findings support the hypothesis that neurological features are present in all types of cretins, and are the consequence of maternal and fetal hypothyroxinemia due to severe iodine deficiency. The clinical manifestations of the cretins were subsequently modified by the length and severity of postnatal iodine deficiency and hypothyroidism.
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PMID:Endemic cretinism in Thailand: a multidisciplinary survey. 936 97

Isolated sulphite oxidase deficiency is a rare metabolic disorder characterised by neurological abnormalities, lens subluxation and seizures. Inheritance is autosomal recessive. We report two siblings with onset of clinical symptoms at 6 months of age, progressing to severe mental retardation, spasticity and seizures which were difficult to control. One of the siblings had lens subluxation. Diagnosis is made upon the increased levels of urinary sulphite, and high plasma S-sulphocysteine and thiosulphate levels. No treatment is known to be of help. Prenatal diagnosis is possible from the analysis of uncultured chorionic villus material for sulphite oxidase.
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PMID:Sulphite oxidase deficiency--a report of two siblings. 940 66

Nine affected individuals are described from a large extended Pakistani family manifesting a syndrome characterized by a triad of varying degrees of spasticity, severe mental retardation, and visual impairment resulting from tapetoretinal degeneration. In all cases, the parents were at least first cousins, since there was complex consanguinity within the pedigree. The clinical features differ from previously reported syndromes involving pigmentary retinal degeneration and appear to represent a new recessively inherited neurodegenerative condition. Linkage to a 4-5 cM-region between markers D15S211 and D15S152 on 15q24 has been established by autozygosity mapping.
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PMID:A syndrome of severe mental retardation, spasticity, and tapetoretinal degeneration linked to chromosome 15q24. 954 91

Neural cell adhesion molecules (CAM) play important roles in neural development, neurite outgrowth, axonal guidance, fasciculation and synapse formation. Neuropathological studies of X-linked hydrocephalus (XLH) associated with L1 CAM mutations emphasize marked hypoplasia of the pyramidal tract, agenesis of the corpus callosum and septum pellucidum, and a thin cerebral mantle with hypoplastic white matter, but there are no detailed studies of the cerebral cortex in the literature. We report clinical, neuroimaging, and neuropathological findings in three boys with XLH. All had severe congenital hydrocephalus with marked thinning of the cerebral mantle and severe development disabilities. The brain specimens from the three boys showed both pachygyria and polymicrogyria, hypoplasia of the medullary pyramids, hypoplasia of the corpus callosum, small anterior commissure, hypoplasia and poorly differentiated hippocampi. A small but patent aqueduct was present in all three brains. Despite the extensive cerebral malformations, the cortex in all three brains showed normal-appearing laminar cortical neuronal architecture and absence of gliosis. In XLH, it is likely that the poor developmental outcome of spasticity, contractures and severe mental retardation results from a disturbance of neuronal connectivity, fasciculation, and synapse formation rather than aqueductal stenosis, increased intracranial pressure, or abnormal neuroblast migration.
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PMID:The pachygyria-polymicrogyria spectrum of cortical dysplasia in X-linked hydrocephalus. 992 16

Heterozygous mutations in the X-linked MECP2 gene cause Rett syndrome, a severe neurodevelopmental disorder of young females. Only one male presenting an MECP2 mutation has been reported; he survived only to age 1 year, suggesting that mutations in MECP2 are male lethal. Here we report a three-generation family in which two affected males showed severe mental retardation and progressive spasticity, previously mapped in Xq27.2-qter. Two obligate carrier females showed either normal or borderline intelligence, simulating an X-linked recessive trait. The two males and the two obligate carrier females presented a mutation in the MECP2 gene, demonstrating that, in males, MECP2 can be responsible for severe mental retardation associated with neurological disorders.
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PMID:A mutation in the rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males. 1098 43

Mutations in the MECP2 (methyl-CpG-binding protein 2) gene are known to cause Rett syndrome, a well-known and clinically defined neurodevelopmental disorder. Rett syndrome occurs almost exclusively in females and for a long time was thought to be an X-linked dominant condition lethal in hemizygous males. Since the discovery of the MECP2 gene as the cause of Rett syndrome in 1999, MECP2 mutations have, however, also been reported in males. These males phenotypically have classical Rett syndrome when the mutation arises as somatic mosaicism or when they have an extra X chromosome. In all other cases, males with MECP2 mutations show diverse phenotypes different from classical Rett syndrome. The spectrum ranges from severe congenital encephalopathy, mental retardation with various neurological symptoms, occasionally in association with psychiatric illness, to mild mental retardation only. We present a 21-year-old male with severe mental retardation, spastic tetraplegia, dystonia, apraxia and neurogenic scoliosis. A history of early hypotonia evolving into severe spasticity, slowing of head growth, breathing irregularities and good visual interactive behaviour were highly suggestive of Rett syndrome. He has a de novo missense mutation in exon 3 of the MECP2 gene (P225L). The clinical spectrum and molecular findings in males with MECP2 mutations are reviewed.
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PMID:Neurodevelopmental disorders in males related to the gene causing Rett syndrome in females (MECP2). 1261 69

Canavan disease (CD) is an inherited leukodystrophy, caused by aspartoacylase (ASPA) deficiency, and accumulation of N-acetylaspartic acid (NAA) in the brain. The gene for ASPA has been cloned and more than 40 mutations have been described, with two founder mutations among Ashkenazi Jewish patients. Screening of Ashkenazi Jews for these two common mutations revealed a high carrier frequency, approximately 1/40, so that programs for carrier testing are currently in practice. The enzyme deficiency in CD interferes with the normal hydrolysis of NAA, which results in disruption of myelin and spongy degeneration of the white matter of the brain. The clinical features of the disease are macrocephaly, head lag, progressive severe mental retardation, and hypotonia in early life, which later changes to spasticity. A knockout mouse for CD has been generated, and used to study the pathophysiological basis for CD. Findings from the knockout mouse indicate that this monogenic trait leads to a series of genomic interaction in the brain. Changes include low levels of glutamate and GABA. Microarray expression analysis showed low level of expression of GABA-A receptor (GABRA6) and glutamate transporter (EAAT4). The gene Spi2, a gene involved in apoptosis and cell death, showed high level of expression. Such complexity of gene interaction results in the phenotype, the proteome, with spongy degeneration of the brain and neurological impairment of the mouse, similar to the human counterpart. Aspartoacylase gene transfer trial in the mouse brain using adenoassociated virus (AAV) as a vector are encouraging showing improved myelination and decrease in spongy degeneration in the area of the injection and also beyond that site.
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PMID:Canavan disease: a monogenic trait with complex genomic interaction. 1456 59

Canavan's disease is an autosomal recessive disorder caused by aspartoacylase deficiency. The deficiency of aspartoacylase leads to increased concentration of N-acetylaspartic acid in brain and body fluids. The failure to hydrolyze N-acetylaspartic acid causes disruption of myelin, resulting in spongy degeneration of the white matter of the brain. The clinical features of the disease are hypotonia in early life, which changes to spasticity, macrocephaly, head lag, and progressive severe mental retardation. Although Canavan's disease is panethnic, it is most prevalent in the Ashkenazi Jewish population. Research at the molecular level led to the cloning of the gene for aspartoacylase and development of a knockout mouse for Canavan's disease. These developments have afforded new tools for research in the attempts to understand the pathophysiology of Canavan's disease, design new therapies, and explore methods for gene transfer to the central nervous system.
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PMID:Molecular basis of Canavan's disease: from human to mouse. 1457 38

Neurological findings, motor symptoms, mental abnormality and dysarthria were examined in 28 children with lesions in the thalamus, putamen, and/or peri-Rolandic area. The thalamus and putamen were involved in eight, and only the thalamus in ten of the children. Most of these 18 children had mild disabilities; they did not have severe mental retardation and could walk alone, speak words, and grasp an object. Dominant flexion of the hips was observed in many of the children who could walk. Two-thirds of these children had athetotic involuntary movement and the remaining had gross or fine motor abnormalities although they had no involuntary movement. In most of these children, reaching patterns were abnormal and were affected by shoulder retraction. Their abnormal movements were thought to be inappropriate muscle activity brought about by voluntary movements. In the remaining ten children, the thalamus, putamen, and peri-Rolandic area were all involved. Many had severe disabilities such as severe mental retardation and the inability to sit, speak words, or grasp an object. All had athetotic involuntary movements. Three children had spasticity of the lower extremities. Five children with severe disabilities and no spasticity were thought to have apparent weakness with athetosis.
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PMID:Clinical profiles of children with cerebral palsy having lesions of the thalamus, putamen and/or peri-Rolandic area. 1513 Jun 88

Metabolic diseases of the nervous system vary considerably in their clinical and pathological aspects. In neurological presentations of these disorders dominate mental retardation and epileptic syndrome. We have studied 27 patients of age from 3 months to 3 years: PKU -- 15 cases; homocystinuria -- 4; hyper-prolinemia -- 1; methylmalonic acidemia -- 5 and combined disorders -- 2. Epileptic syndrome was revealed in 21 patients, mental retardation in 1, spasticity in 5 and ataxia in 1 patient. Epileptic syndrome was presented with generalized seizures (grand mal -- 6 cases, myoclonic absences -- 13 cases) and partial seizures (simple motor -- 2 cases). Investigations did not found reliable correlations between certain forms of enzymophaties and EEG patterns. Patients were treated by pathogenic (dietary management with protein-modified diet and vitamin therapy) and symptomatic (anticonvulsants) treatment. We have achieved the positive therapeutic effect by pathogenic and anticonvulsive treatment in 11 patients. All these patients were from the first group (1-3 year). The best outcome was observed in the cases of the early diagnosed PKU. The most severe mental retardation and resistant epilepsy were revealed in patients with combined disorders of metabolism and vitamin-non-responsive forms of MMA and HCS.
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PMID:[Peculiarities of epileptic syndrome in children with metabolic disorders of nervous system]. 1636 68


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