Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rett syndrome (RTT) is a mostly sporadic disorder of developmental regression, with loss of speech and purposeful hand use, microcephaly and seizures. It affects 1 in 10 000-15 000 females. RTT is caused by mutations in the MECP2 gene, which is located in Xq28 and subject to X inactivation. MECP2 encodes a methyl-CpG-binding protein that binds to 5-methyl-cytosine in DNA through its methyl-binding domain. Recruitment of a transcriptional silencing complex through MeCP2's transcriptional repression domain results in histone deacetylation and chromatin condensation. To study the effects of two common truncating RTT mutations (R168X and 803delG), we examined mutant MeCP2 expression and global histone acetylation levels in clonal cell cultures from a female RTT patient with the mutant R168X allele on the active X chromosome, as well as in cells from a male hemizygous for the frameshift mutation 803delG (V288X). Both mutant alleles generated stable RNA transcripts, but no intact MeCP2 protein was detected with an antibody against the C-terminal region of MeCP2. Western blots with antibodies against acetylated histones H3 and H4 revealed that H4, but not H3, was hyperacetylated. By using antibodies against individual acetylated lysine residues, the observed H4 hyperacetylation was attributed to increased acetylation of lysine 16. Therefore, expression of endogenous truncating MECP2 alleles, in the absence of wild-type MeCP2 protein, is specifically associated with an increase in the mono-acetylated histone isoform H4K16. This observed effect may result in over-expression of MeCP2 target genes and, thus, play a role in the pathogenesis of RTT.
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PMID:MECP2 truncating mutations cause histone H4 hyperacetylation in Rett syndrome. 1133 19

Rett syndrome (RS) is a particular neurodevelopmental disorder in which symptoms develop in early infancy and manifests particular symptoms at certain ages. Two girls aged 4.5 and 2.5-years-old were admitted with complaints of seizures, regression of language, psychomotor development, and autistic behavior. They had fulfilled the criteria of classic RS. Lamotrigine was used in the treatment of the convulsions. After lamotrigine therapy, the convulsions were successfully controlled and the stereotyped hand movements and autistic behaviors markedly decreased. We would like to stress that, aside from convulsion, abnormal signs of the syndrome such as stereotyped hand movements and autistic behaviors might also be improved with lamotrigine, but detailed and controlled studies should be performed to identify whether lamotrigine has any positive effects in RS.
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PMID:Lamotrigine in two cases of Rett syndrome. 1137 3

From November 1982 to May 1999, 28 children with Rett syndrome were followed-up for a medium period of 6 years and 2 months. Regression of developmental milestones started at the age between 5 and 20 months. Nineteen cases of typical Rett syndrome had uneventful pre and perinatal periods, loss of previously acquired purposeful hand skills, mental and motor regression and developed hand stereotypies; sixteen had head growth deceleration and 12 gait apraxia. Nine patients were atypical cases, 2 formes frustres, 2 congenital, 3 with early seizure onset, 1 preserved speech and 1 male. Epilepsy was present in 21 patients, predominantly partial seizures and the drug of choice was carbamazepine (15 patients). In the initial evaluation most patients were distributed on Stages II and III and on follow-up on Stages III and IV. Three children died.
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PMID:[Rett syndrome: retrospective and prospective study of 28 patients]. 1146 Jan 88

Rett syndrome consists of a highly complex but consistent set of clinical signs and symptoms. Clinical characteristics consist of microcephaly, delayed psychomotor development, autistic behavior, stereotyped hand-washing, and seizures. Over a period of 14 years (1987-2000), 7 patients with Rett syndrome were evaluated at the Out Patient Unit, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. All seven patients were females aging 1 1/2 to 5 years old when diagnosis was established. All were appearently normal at birth and had developmental regression after a period of time. All of them developed microcephaly, autistic features, seizures, and stereotyped hand-washing-movement. Five of seven patients (71.42%) developed episodic hyperventilation. All cases had abnormal electroencephalogram. Computer tomography scan were examined in 3 cases which were normal while magnetic resonance imaging were studied in 2 cases and was abnormal in one.
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PMID:Rett syndrome in Thai female girls: clinical studies. 1152 81

The syndrome of brain atrophy in girls described by Andreas Rett in 1966 [Rett, Wien Klin Wochenschr, 1966;116:723-726] was brought to the attention of the English-speaking world by Hagberg et al. in 1983 [Hagberg et al., Ann Neurol, 1983;14:471-479]. Four clinical stages after the age of 6 months were described in classical cases of Rett syndrome (RS), namely early onset stagnation at 6 months to 1(1/2) years, the rapid destructive stage at 1-3 years, the pseudo-stationary stage from pre-school to school years, and the late motor deterioration stage at 15-30 or more years. The rapid destructive stage causes profound dementia with loss of speech and hand skills, stereotypic movements, ataxia, apraxia, irregular breathing with hyperventilation while awake, and frequently seizures. Most cases are isolated in their families, apart from identical twins. However, linkage studies in rare familial cases suggested a critical region at Xq28. In 1999 American investigators found several mutations in the X-linked gene MECP2 encoding Methyl-CpG-binding protein 2 in a proportion of Rett patients. The protein MeCP2 can bind methylated DNA and when mutated may interfere with transcriptional silencing of other genes and result in abnormal chromatin assembly. Many different mutations of the protein are being studied in humans and in mice. Neuropathological studies have shown decreased brain growth and decreased size of individual neurons, with thinned dendrites in some cortical layers, and abnormalities in substantia nigra, suggestive of deficient synaptogenic development, probably starting before birth. Electrophysiology demonstrates progressively abnormal electroencephalograms (EEG) in the first three stages of the syndrome, with some subsequent improvement and occurrence of pseudoseizures. Neurometabolic factors are discussed in detail, particularly reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. Autonomic dysfunction is described, particularly reduced vagal and overactive sympathetic activity. Neuro-imaging may be required for further investigation, as shown in the differential diagnosis.
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PMID:Importance of Rett syndrome in child neurology. 1173 40

Neuroimaging is a key instrument for determining structural and in vivo functional status of the brain, non-invasively. Multiple approaches can now determine aspects of anatomic and neurochemical changes in brain, and have been utilized effectively in Rett Syndrome patients to understand the biological basis of this neurodevelopmental disorder. Studies performed at our institute include volumetric analyses of MRI, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), cerebral blood flow measurements with MRI, and positron emission tomography scans (PET). These studies have provided considerable insight into mechanisms underlying the clinical features of this disease. Volumetric analyses suggest that decreased brain volume in RS results from global reductions in both gray and white matter of the brain. A selective vulnerability of the frontal lobes is evidenced by the preferential reduction of blood flow, increased choline and reduced n-acetyl aspartate (NAA) by MRS, and increased glucose uptake in these same regions as shown by ((18)F)-fluorodeoxyglucose (FDG) PET scans. We hypothesize that the increased glucose uptake relates to increased glutamate cycling in synapses. The resulting neuroexcitotoxic injury to the developing brain contributes to the seizures, behavioral disturbance and respiratory irregularities commonly seen in phases 1 and 2 of this disorder.
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PMID:Neuroimaging studies in Rett syndrome. 1173 44

The investigation of parameters that might influence the neurological evolution of Rett syndrome might also yield new information about its pathogenic mechanisms. Oxidative stress caused by oxygen free radicals is involved in the neuropathology of several neurodegenerative disorders, as well as in stroke and seizures. To evaluate the free radical metabolism in Rett syndrome, we measured red blood cell antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) and plasma malondialdehyde, as lipid peroxidation marker in a group of patients with Rett syndrome. No significant differences were observed in erythrocyte glutathione peroxidase, glutathione reductase and catalase activities, between the Rett syndrome patients and the control group. Erythrocyte superoxide dismutase activities were significantly decreased in Rett syndrome patients (P<0.001) compared with the control group. Plasma malondialdehyde concentrations were significantly increased in Rett syndrome patients (P<0.001). An unbalanced nutritional status in Rett syndrome might explain the reduced enzyme activity found in these patients. Our results suggest that free radicals generated from oxidation reactions might contribute to the pathogenesis of Rett syndrome. The high levels of malondialdehyde reflect peroxidative damage of biomembranes that may contribute to progressive dementia, impaired motor function, behavioural changes, and seizures, in Rett syndrome. We found a probable relationship between the degree of oxidative stress and the severity of symptoms, which should be further investigated with a larger number of patients in different disease stages.
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PMID:Oxidative stress in Rett syndrome. 1173 81

We report a case of 13-year-old-girl with Rett's syndrome and effectiveness of gastrostomy for severe paradoxical respiration, seizures and abdominal distention. Since the age of 3, she was observed to have typical hand-washing movement and autistic behavior. At the age of 8, she began to have hyperventilation and seizures in awake stage. Her symptoms were worse from year to year. At the age of 13, gastrostomy was done to treat severe abdominal distention. Her symptoms were improve dramatically by the gastric air removal through gastrobutton.
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PMID:A case of effective gastrostomy for severe abdominal distention due to breathing dysfunction of Rett's syndrome: a treatment of autonomic disorder. 1173 82

Neurophysiological evaluations have been widely applied in the study of Rett syndrome (RS) to provide information concerning the developmental aspects of RS; the character and extent of involvement of the central, peripheral, and autonomic nervous system pathways; and evaluation of the clinical symptomatology of RS. The electroencephalogram (EEG) is invariably abnormal and shows characteristic, though not diagnostic, changes: loss of expected developmental features; the appearance of focal, multifocal, and generalized epileptiform abnormalities; and the occurrence of rhythmic slow (theta) activity primarily in the frontal-central regions. Epileptic seizures are reported to occur frequently in RS, and partial and generalized seizures may be experienced by RS girls. However, many events presumed to be seizures have no EEG correlate during video-EEG monitoring, suggesting the possibility of a nonepileptic mechanism. Such monitoring may be necessary to determine appropriate use of antiepileptic drugs. Evoked potentials typically demonstrate intact peripheral auditory and visual pathways and suggest dysfunction of central or "higher" cortical pathways. Somatosensory-evoked potentials may be characterized by "giant" responses, suggesting cortical hyperexcitability. An increased incidence of long QT intervals during electrocardiographic recordings and diminished heart-rate variability, suggesting impairment of the autonomic nervous system, are described in RS. With the discovery of the genetic basis of RS, neurophysiological studies will provide parameters for phenotype-genotype correlations and characterization of animal models.
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PMID:Neurophysiology of Rett syndrome. 1211 29

Prospects for definitive therapeutic intervention for Rett syndrome (RS) have been elevated by the discovery of mutations in the methyl-CpG-binding protein 2 gene (MECP2) in more than 80% of females meeting clinical criteria for this disorder. As such, a review of previous clinical trials, descriptions of the status of clinical management for the prominent medical problems of RS, and a preview of an ongoing clinical trial conducted jointly at the Baylor College of Medicine and the University of Alabama at Birmingham are presented. The conduct of controlled clinical trials requires adherence to diagnostic criteria for RS; stratification by age, stage, and presence of MECP2 mutations; and use of clearly defined outcome measures. Previous clinical trials in RS have been conducted with L-carnitine, the ketogenic diet, and the opiate antagonist, naltrexone. The L-carnitine and naltrexone trials were double blind, placebo-controlled and us ed the motor behavioral analysis described in this review. All failed to provide evidence of dramatic improvements in the clinical features of RS. Specific recommendations are presented for clinical management of growth failure, breathing irregularities, seizures, ambulation, scoliosis, gastrointestinal function, self abuse, and habilitation/education although systematic evaluations of each in the context of RS have not been conducted. The only ongoing trial involves dietary supplementation with folate and betaine and is based on the finding that gene expression of some alleles of the agouti gene could be altered by dietary methyl supplementation. The availability of animal models expressing mutations in MECP2 should enhance the evaluation of innovative therapies for RS.
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PMID:Clinical trials and treatment prospects. 1211 36


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