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

To clarify the relationship between the degree of developmental disturbance and the severity of epilepsy in Angelman syndrome, we investigated 11 patients and measured both clinical outcomes and EEG parameters. Seven patients were followed up until after 8 years of age. Eight patients were found to have 15q11-q13 deletions. All patients experienced epileptic seizures and all but one displayed non-convulsive status epilepticus (NCSE) during the period of observation. Epileptic seizures, including NCSE, disappeared by around 8 years of age. In addition, specific epileptic discharges, as measured by EEG, tended to subside with age. Although development seemed almost normal or only slightly delayed during the first 6 months of life, all patients eventually developed severe retardation. Two patients displayed very severe retardation and were unable to comprehend language or walk independently at the last follow-up. Only one patient was able to speak a few meaningful words. In one of the most severely affected patients, who showed the earliest onset of seizures and NCSE, it is possible that the repetitive bouts of NCSE might be responsible for the severe developmental outcome. However, the other patient with particularly severe retardation did not experience NCSE, while the patient with the most favorable outcome had repetitive episodes of NCSE. Therefore, we conclude that the severity of developmental disturbance in Angelman syndrome is not necessarily related to the degree of epilepsy. However, intensive therapy for NCSE might still be justified because there are some patients in whom NCSE results in a transient and sometimes permanent decline in mental and motor functioning.
 ...
PMID:Relationship between severity of epilepsy and developmental outcome in Angelman syndrome. 1566 47

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurobehavioral syndromes that are caused by deficiency of gene expression from paternally or maternally derived homologues on chromosome 15q11-q13, respectively. Clinical and genetic heterogeneities are common in both syndromes and they are now regarded as 'sister genetic imprinting syndromes'. This study aimed to describe and compare the electroclinical characteristics of seizures between PWS and AS, and to try to explore the possible mechanisms of epileptogenesis in these two syndromes. Fifty patients with genetically documented PWS and 18 patients with a putative diagnosis of AS were included in this study. These patients were diagnosed on the basis of characteristic physical findings and their neurobehavioral phenotype, as well as cytogenetic and molecular studies. Epileptic seizures were present in 16 of 18 patients with AS, but in only eight of 50 patients with PWS. Using electroencephalography (EEG), the most characteristic findings for AS were rhythmic 2-3 Hz delta waves of high-amplitude that were maximal over the frontal regions, and 3-4 Hz spikes and sharp wave runs posteriorly. These were never seen in PWS. Patients with AS had a much higher incidence of seizures with characteristic EEG findings, similar to those seen in mice that are deficient in a single gene (UBE3A) that displays regional brain-specific imprinting in humans and mice. In this series, cases with no detectable cytogenetic or molecular defect at the AS locus displayed similar AS phenotype, seizure severity and EEG abnormalities compared to those with such a defect. Thus, the UBE3A gene is presumed to be potentially involved in the epileptogenesis of AS. It is also possible that UBE3A and another gene located nearby, gamma-aminobutyric receptorbeta3 subunit, may interact in some way, and result in the severe epilepsy seen with AS. Some patients with PWS and AS share the common EEG features of persistent high-amplitude 4-6 Hz activity in recordings during sleep, and while awake. The significance of such EEG findings needs further experience to clarity.
 ...
PMID:Electroclinical characteristics of seizures-comparing Prader--Willi syndrome with Angelman syndrome. 1566 48

While there is an abundance of literature describing the association of chromosome aberrations with epilepsy, only a few refer to the detailed features of epilepsy. It is important to investigate the associations between specific chromosome abnormalities and features of epilepsy to identify genes involved in epilepsy and treat them more effectively. We investigated the correlation between specific chromosome aberrations and epilepsy by sending questionnaires to the members of Kyoto Multi-institutional Study Group of Pediatric Neurology. Seventy-six patients were collected from 10 institutions. Chromosome abnormalities included: Down syndrome (n = 19); Angelman syndrome (n = 8); Prader-Willi syndrome (n = 4); 4p- syndrome (n = 3); 1q- syndrome (n = 2); 5p- syndrome (n = 2); Miller-Dieker syndrome (n = 2); 18q- syndrome; (n = 2); Klinefelter syndrome; (n = 2); and 32 other individual chromosomal aberrations. Overall, the severity of mental retardation correlated with the severity of epilepsy. We could abstract characteristic features of epilepsy in some syndromes. In Angelman and Prader-Willi syndromes, febrile seizures occurred frequently, the onset of epilepsy was in early childhood and seizure phenotype was multiple. Paroxysmal discharge of the occipital region and diffuse high voltage slow wave on electroencephalography were characteristic in Angelman syndrome. In Down syndrome, West syndrome and focal epilepsy were common and the prognosis of epilepsy in West syndrome with Down syndrome was good. In 4p- syndrome, febrile seizures were often seen, and unilateral or generalized clonic or tonic-clonic status epilepticus were characteristic. For the other chromosomal aberrations investigated here, the patient numbers were too small to abstract common features of epilepsy.
 ...
PMID:Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy. 1566 53

Angelman syndrome is a genetic disorder caused by defects in the maternally inherited imprinted domain located on chromosome 15q11-q13. Most patients with Angelman syndrome present with severe mental retardation, characteristic physical appearance, behavioral traits, and severe, early-onset epilepsy. We retrospectively reviewed the medical histories of 37 patients, all with the molecular diagnosis of Angelman syndrome and at least three years of follow-up in our neurology department, for further information about their epilepsy: age of onset, type of seizures initially and during follow-up, EEG recordings, treatments and response. The molecular studies showed 87% deletions de novo, 8% uniparental, paternal disomy, and 5% imprinting defects. The median age at diagnosis was 6.5 years, with 20% having begun to manifest febrile seizures at an average age of 1.9 years. Nearly all (95%) presented with epilepsy, the majority under the age of three (76%). The most frequent seizure types were myoclonic, atonic, generalized tonic-clonic and atypical absences. At onset, two patients exhibited West syndrome. EEG recordings typical of Angelman syndrome were found in 68%. Normalization of EEG appeared in 12 patients after nine years. Control of epileptic seizures improved after the age of 8.5 years. The most effective treatments were valproic acid and clonazepam. We conclude that epilepsy was present in nearly all of our cases with Angelman syndrome, and that the EEG can be a useful diagnostic tool. On comparing the severity of epilepsy with the type of genetic alteration, we did not find any statistically significant correlations.
 ...
PMID:Analysis of the characteristics of epilepsy in 37 patients with the molecular diagnosis of Angelman syndrome. 1637 55

Although the pathogenesis of cerebral aneurysms has been studied intensively, it is yet poorly understood. However, a genetic predisposition to this pathology has been often suspected. We describe a patient with both intracranial aneurysm and Angelman syndrome. Angelman syndrome is characterized by severe mental retardation, inappropriate laughter, absent speech, dysmorphic facial features and seizures. It is due to genetic abnormalities of chromosome 15. Cerebral aneurysms are sometimes associated with inherited diseases like autosomal dominant polycystic kidney disease. Moreover several candidate genes have been analysed, to search for genetic variants which might be associated with the occurrence of intracranial aneurysms. Our question is: is the association described in our observation fortuitous or do these diseases share a same genetic predisposition? Our observation also supports the hypothesis of a genetic participation in the genesis of cerebral aneurysms.
 ...
PMID:[Angelman syndrome and intracranial aneurysm: fortuitous association or commune genetic predisposition?]. 1580 34

Epilepsy is among the most frequent finding in many chromosome aberrations. While most chromosome aberrations can be associated with different seizure types, there are few aberrations which feature specific seizures and EEG patterns. Among the 400 different chromosomal imbalances described with seizures and EEG abnormalities, eight have a high association with epilepsy. These comprise: the monosomy 1p36, Wolf-Hirschhorn syndrome (4p-), Angelman syndrome, Miller-Dieker del 17p13.3, the inversion duplication 15 syndrome, ring 20 and ring 14 syndromes, Down's syndrome. These chromosomal regions where aberrations have an evident association with epilepsy may be useful targets for gene hunters. On the other hand, a better characterisation of epileptic syndrome in these disorders may lead to a better and specific treatment.
 ...
PMID:[Epilepsy in chromosome aberrations]. 1580 38

The homozygous knockout mouse for the beta3 subunit of the GABAA receptor has been proposed as a model for the neurodevelopmental disorder, Angelman syndrome, based on phenotypic similarities of craniofacial abnormalities, cognitive defects, hyperactivity, motor incoordination, disturbed rest-activity cycles, and epilepsy. Since most children with Angelman syndrome are autosomal heterozygotes of maternal origin, apparently through genomic imprinting, we used gabrb3-deficient heterozygote mice of defined parental origin to investigate whether this phenotype is also maternally imprinted in mouse. Whole brain extracts showed greatly reduced beta3 subunit levels in male mice of maternal origin but not in male mice of paternal origin. Females of both parental origin showed greatly reduced beta3 subunit levels. Heterozygotes did not exhibit hyperactive circling behavior, convulsions, or electrographically recorded seizures. EEGs showed qualitative differences among heterozygotes, with male mice of maternal origin demonstrating more abnormalities including increased theta activity. Ethosuximide inhibited theta bursts, suggesting an alteration in the thalamocortical relay. Carbamazepine induced EEG slowing in males and EEG acceleration in females, with a larger effect in paternal-origin heterozygotes. Evidence thus suggests both parent-of-origin and gender-related components in developmental regulation of beta3 expression, in particular, that the maternally-derived male heterozygote may carry a developmental modification resulting in less beta3 protein, which may reflect partial genomic imprinting of the gabrb3 gene in mice.
 ...
PMID:GABAA receptor beta3 subunit gene-deficient heterozygous mice show parent-of-origin and gender-related differences in beta3 subunit levels, EEG, and behavior. 1587 4

Angelman syndrome (AS) is a genetic disorder with characteristic clinical and EEG findings. We report here the results of long-term follow-up studies on the epileptic seizures and EEG findings of 23 cases of deletion type AS confirmed by FISH analysis, including seven cases previously reported by Matsumoto et al. in 1992. The age at last follow-up in 23 patients was from 1 to 37 years of age (average: 18.0 years), with 10 patients (43.5%) in their 20s, and five over 30. Epileptic seizures were seen in all patients, and the age at seizure onset ranged from 3 to 50 months (average: 21.7 months). Status epilepticus was seen in 11 patients (47.8%). The percentages of cases seizure-free for more than 3 years were 25% (4/16) at 10 years of age, 70% (7/10) at 20, and 80% (4/5) at 30. The EEG findings were classified into six patterns according to the previous report: N (no spike, including focal slow waves), HVS (diffuse high-voltage slow bursts with or without spikes), F (focal spikes or multifocal spikes), S (diffuse spike and waves), C (continuous diffuse spike and waves), Hy (hypsarrythmia or hypsarrhythmia like waves). Hy was noted at ages 0-2 years in two cases. C was observed from the ages 2 to 15 years, being most frequently noted at 3-6 years of age, and it was never seen after 16 years of age. S was observed from ages 1 to 21 years. F was seen from 2 to 21 years of age, and most frequently during the ages of 2-7 years. HVS was seen from 0 years, and still remained after the age of 20. After 22 years of age, all patients showed N pattern including focal slow waves. One of the two patients who had bilateral frontal dominant delta slow waves in their 30s, had a recent seizure. Even if the spikes disappear with age, when bi-frontal focal slow waves remain, seizures may occur even in patients over 30.
 ...
PMID:Evolution of seizures and electroencephalographical findings in 23 cases of deletion type Angelman syndrome. 1596 70

The chromosome region 15q11q13 is known for its instability, and many rearrangements may occur in this imprinted segment: deletions associated either with Angelman syndrome (AS) or with Prader-Willi syndrome (PWS), according to parental origin; translocations; inversions; and supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) constitute the most common of the heterogeneous group of the extra structurally abnormal chromosomes, and their presence results in tetrasomy 15p and partial tetrasomy 15q. Inv dup(15), containing the Prader-Willi/Angelman syndrome region, are associated with altered behaviour, developmental delay/mental retardation, and seizures/epilepsy. Clinicians should suspect this syndrome in any infant/child with early central hypotonia, minor dysmorphic features, developmental delay, autism or autistic-like behaviour, and who subsequently develops hard to control seizures/epilepsy. Diagnosis is confirmed by standard cytogenetic techniques and FISH analysis. Although, about 100 cases have been reported to date, limited data are available on the natural history. To obtain better information on diagnosis and outcome in a clinical setting, we reviewed the available literature on clinical and behavioural phenotype of inv dup(15) syndrome.
 ...
PMID:The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. 1602 54

We retrospectively reviewed the medical records of neonates with chromosomal abnormalities and epilepsy who had been admitted to the neonatal intensive care unit (NICU) and followed up at the outpatient clinic of Dokkyo University School of Medicine. Chromosomal anomalies were diagnosed in 128 of 5789 patients admitted from 1978 through 2001. Seventy-one neonates had trisomy 21, 29 had trisomy 18, 8 had trisomy 13, and 20 had other chromosomal anomalies. Seizures occurred in five patients with trisomy 21 and in one patient each with trisomy 18, 6q-, 13q-, 21q-, and mosaicism trisomy 13. Two patients with 4p- [Wolf-Hirschhorn syndrome] were admitted to the NICU, but were not followed up at our outpatient clinic. The boy with 6q- (46,XY,-6, +der(6)t(6;11)(q25.1;q23.3)mat) had agenesis of the corpus callosum and multiple congenital anomalies as well as intractable epilepsy. The girl with 13q- (46, XX, t(2,4)(q24.2;p14), del (13)(q21.2q31.2)) had infantile spasms at 12 months, which were well controlled with nitrazepam and vitamin B6. The girl with mosaic trisomy 8q; (46, XX, der(8) (qter-->q11.2::p23.3-->qter)/46, XX), was not born at our hospital, but showed unique clinical features. She had intractable epilepsy characterized by episodes of vomiting and staring with astatic seizures. Computed tomography of the brain revealed bilateral calcification in the globus pallidus, associated with bursts of high-amplitude slow waves on electroencephalography. One of the two patients with del(15)(q12)[Angelman syndrome] had giant-amplitude visual evoked potential, suggesting hyperexcitability of the visual cortex.
 ...
PMID:An analysis of epilepsy with chromosomal abnormalities. 1602 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>