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)

Monoaminergic neurotransmission plays an important role in the regulation of neuronal network excitability and seizure activity. Therapeutic inhibition of the mitochondrial enzyme monoamine oxidase A (MAO-A), which is involved in the degradation and inactivation of monoaminergic neurotransmitters, has been shown to confer a potent anticonvulsant effect. These and other findings suggest a possible role of the X-linked MAO-A gene in epileptogenesis. Therefore, our study was designed to test for an association between a novel MAO-A gene promoter polymorphism and common subtypes of idiopathic generalized epilepsy (IGE). The length of a 30-bp repetitive sequence approximately 1.2 kb upstream of the ATG initiation codon was assessed in 126 patients with juvenile myoclonic epilepsy (JME), 122 patients with idiopathic absence epilepsy (IAE), and 248 healthy controls of German descent. Both sexes were analyzed separately. Although we observed a trend towards a lower number of heterozygotes carrying the 3 and 4 copy alleles in female IAE patients (chi2 = 3.813, df = 1, P = 0.053), allele frequencies did not deviate significantly between patients and controls. Thus, our results do not provide evidence for a contribution of the functional MAO-A gene promoter polymorphism to the pathogenesis of common IGE subtypes.
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PMID:Association analysis between a regulatory-promoter polymorphism of the human monoamine oxidase A gene and idiopathic generalized epilepsy. 1075 1

Colpocephaly is an abnormal congenital enlargement of the occipital horns of the lateral ventricles, which has typically been associated with learning disability, seizures, and motor and visual abnormalities. This study describes familial colpocephaly in two siblings with different fathers in a Dominican family. There were no other neurological problems in their relatives. Child 1 is a 7-year-old girl, who has had partial epileptic seizures since 4 years of age. She attends a mainstream school. She has coloboma and chorioretinic atrophy in her right eye and a right microphthalmia. MRI revealed colpocephaly and hypogenesis of the corpus callosum. Her brother, aged 2 years 8 months showed a mild delay in speech acquisition. He has had three febrile convulsions and two non-febrile tonic-clonic seizures since 6 months of age. Neurological and ophthalmological examinations were normal. MRI documented colpocephaly with right occipital horn prevalence. There are only two literature reports of genetically transmitted colpocephaly hypothesised in two identical twins and in two brothers. In the children in this study, a genetic basis for colpocephaly is confirmed. We hypothesised a maternal transmission with X-linked or autosomal dominance with an incomplete penetrance model of inheritance.
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PMID:Colpocephaly in two siblings: further evidence of a genetic transmission. 1079 69

Periventricular nodular heterotopia (PNH) is considered a distinct entity in relation to the other forms of neuronal migration disorders (NMD), because PNH patients usually have normal neurological and mental examination results. We report the case of a 48-year-old woman with bilateral periventricular nodular heterotopia associated with epilepsy, coeliac disease, palatoschisis and other dysmorphic features. Her intelligence quotient (I.Q.) and the results of a neurological examination were normal, but she suffered from a drug-resistant epileptic syndrome characterised by predominantly generalised and sporadic partial seizures. It has recently been suggested that an X-linked dominant inheritance may play a role in bilateral periventricular nodular heterotopia, and it is thought that a genetic defect is probably responsible for coeliac disease. In our patient, a genetic disorder may have produced both diseases and the dysmorphic syndrome, although the coexistence of PNH, epileptic seizures, coeliac disease and palatoschisis could be coincidental. Further observations are needed to ascertain whether the simultaneous presence of these disorders is simply an unusual association of unrelated pathologies or a new and distinct pathological entity.
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PMID:Bilateral periventricular nodular heterotopia associated with coeliac disease and palatoschisis. 1093 74

X-linked mental retardation is a very common condition that affects approximately 1 in 600 males. Despite recent progress, in most cases the molecular defects underlying this disorder remain unknown. Recently, a study using the candidate gene approach demonstrated the presence of mutations in PAK3 (p21-activating kinase) associated with nonspecific mental retardation. PAK3 is a member of the larger family of PAK genes. PAK proteins have been implicated as critical downstream effectors that link Rho-GTPases to the actin cytoskeleton and to MAP kinase cascades, including the c-Jun amino-terminal kinase (JNK) and p38. We screened 12 MRX pedigrees that map to a large region overlying Xq21-q24. Mutation screening of the whole coding region of the PAK3 gene was performed by using a combination of denaturing gradient gel electrophoresis and direct sequencing. We have identified a novel missense mutation in exon 2 of PAK3 gene (R67C) in MRX47. This confirms the involvement of PAK3 in MRX following the report of a nonsense mutation recently reported in MRX30. In the MRX47 family, all affected males show moderate to severe mental retardation. No seizures, statural growth deficiency, or minor facial or other abnormal physical features were observed. This mutation R67C is located in a conserved polybasic domain (AA 66-68) of the protein that is predicted to play a major role in the GTPases binding and stimulation of Pak activity.
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PMID:Missense mutation in PAK3, R67C, causes X-linked nonspecific mental retardation. 1094 56

Rab GDP dissociation inhibitor alpha (Rab GDIalpha) is a regulator of the Rab small G proteins implicated in neurotransmission, and mutations of Rab GDIalpha cause human X-linked mental retardation associated with epileptic seizures. In Rab GDIalpha-deficient mice, synaptic potentials in the CA1 region of the hippocampus displayed larger enhancement during repetitive stimulation, which was apparently opposite to the phenotype of Rab3A-deficient mice. Furthermore, the Rab GDIalpha-deficient mice showed hypersensitivity to bicuculline, an inducer of epileptic seizures. These results suggest that Rab GDIalpha plays a specialized role in Rab3A recycling to suppress hyperexcitability via modulation of presynaptic forms of plasticity.
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PMID:Role of rab GDP dissociation inhibitor alpha in regulating plasticity of hippocampal neurotransmission. 1102 56

Isolated Lissencephaly Sequence (ILS) and Double-Cortex Syndrome (DC) are neuronal heterotopias caused by developmental defects in neuronal precursor cell migration. We report on the clinical and genetic assessment of a German pedigree with DCIILS. Affected males showed clinical symptoms typical of lissencephaly, i.e. seizures, severe mental retardation and extensive physical disability starting in the early postnatal period. Females, however, displayed a milder phenotype with epileptic seizures being the only clinical symptom of note. The MR imaging of a male ILS patient showed a smooth cortex with pachygyria, hydrocephalus and a diffuse, broad distribution of grey matter throughout the brain. In the affected female, a double cortex syndrome in the form of a subcortical bilateral band of grey matter was evident by MR imaging. The molecular and genetic basis of DC/ILS is associated with mutations in the X-linked doublecortin gene (DCX). The genetic assessment of the family revealed a novel missense mutation 211 G-->T in DCX exon 2 in affected family members. This mutation cosegregated with the clinical symptoms and resulted in a non-conservative amino acid substitution A71S. DCX is a microtubule-associated phosphoprotein and mutations in DCX might affect cytoskeletal dynamics and the regulation of cell migration.
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PMID:Isolated lissencephaly sequence and double-cortex syndrome in a German family with a novel doublecortin mutation. 1107 Nov 44

Focal cortical dysplasias (FCD) and diffuse cortical dysplasias (DCD) are a heterogeneous group of disorders defined by abnormal cerebral cortical cytoarchitecture that are associated with epilepsy. Patients with either DCD or FCD may suffer from a variety of epilepsy subtypes and these are often refractory to most anti-epileptic drugs (AEDs) despite polytherapy. The etiologies of cortical dysplasias (CD) are diverse, and include inherited genetic syndromes such as Miller-Dieker or X-linked lissencephaly, subcortical band heterotopia, and the tuberous sclerosis complex, as well as nongenetic exogenous insults such as hypoxic-ischemic injury, viral or other type of central nervous system infection, or traumatic injury. A large number of FCD cases are idiopathic and very small regions of FCD (microdysgenesis) are now being identified in resected epilepsy specimens. Recent data suggests that nearly 30% of epilepsy specimens evaluated histologically will contain regions of overt or microscopic CD. The mainstay of appropriate therapy for CD remains the standard AEDs or epilepsy surgery. In too few disorders, specific AEDs provide therapeutic advantage in the setting of individual forms of CD. The ketogenic diet may provide seizure control in a subpopulation of patients. In both DCD and FCD, surgical resection can be curative in the appropriately selected patients. Surgical approaches include focal neocortical resections, temporal lobectomy, or larger hemispheric resection procedures.
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PMID:Epilepsy and Cortical Dysplasias. 1109 78

Aicardi syndrome is an X-linked dominant disorder primarily defined by the triad of corpus callosum agenesis, infantile spasms and a pathognomonic lacunar chorioretinopathy. Papillomas of the choroid plexus have been reported in affected patients. We report an Aicardi syndrome patient who had three separate choroid plexus papillomas and associated hydrocephalus. A dizygotic twin was unaffected. Staged resection of the tumors was safely accomplished, with improvement in seizure control. Imaging between procedures revealed rapid tumor growth.
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PMID:Three choroid plexus papillomas in a patient with Aicardi syndrome. A case report. 1112 40

Epileptic seizures are a common feature in Menkes disease, an X-linked genetic disorder of copper metabolism. Details of type of seizures are rarely reported. We report the evolution of infantile spasms in two patients with Menkes disease and the relation with subcutaneous administration of copper-histidine.
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PMID:Infantile spasms and Menkes disease. 1117 54

Rett syndrome is a neurodevelopmental disorder affecting almost exclusively females. It affects approximately one in 15000 females and is characterized by a loss of purposeful hand use, autism, ataxia and seizure. The disorder is usually sporadic, but rare familial cases have also been reported. Recently it has been shown that familial cases are an X-linked dominant disorder and the disease locus maps to Xq28. A candidate gene called methyl-CpG-binding protein 2 was identified from the Xq28 region and was shown to contain mutations in about 77% of Rett syndrome patients. Since the encoded protein was previously shown to be a global transcriptional repressor, undesired expression of yet unidentified genes that are normally repressed is considered to be pathogenic in Rett syndrome.
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PMID:Molecular genetics of Rett syndrome. 1124 98


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