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)

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its gamma-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome.
 ...
PMID:Effect of topiramate on seizures and respiratory dysrhythmia in Rett syndrome. 1560 67

Rett syndrome (RS) is a severe neurodevelopmental disorder that contributes significantly to severe intellectual disability in females worldwide. It is caused by mutations in MECP2 in the majority of cases, but a proportion of atypical cases may result from mutations in CDKL5, particularly the early onset seizure variant. The relationship between MECP2 and CDKL5, and whether they cause RS through the same or different mechanisms is unknown, but is worthy of investigation. Mutations in MECP2 appear to give a growth disadvantage to both neuronal and lymphoblast cells, often resulting in skewing of X inactivation that may contribute to the large degree of phenotypic variation. MeCP2 was originally thought to be a global transcriptional repressor, but recent evidence suggests that it may have a role in regulating neuronal activity dependent expression of specific genes such as Hairy2a in Xenopus and Bdnf in mouse and rat.
 ...
PMID:Rett syndrome: clinical review and genetic update. 1563 68

Rett syndrome (RTT) is a severe neurodevelopmental disorder almost exclusively affecting females and characterized by a wide spectrum of clinical manifestations. Most patients affected by classic RTT and a smaller percentage of patients with the milder form 'preserved speech variant' have either point mutations or deletions/duplications in the MECP2 gene. Recently, mutations in the CDKL5 gene, coding for a putative kinase, have been found in female patients with a phenotype overlapping with that of RTT. Here, we report two patients with the early seizure variant of RTT, bearing two novel CDKL5 truncating mutations, strengthening the correlation between CDKL5 and RTT. Considering the similar phenotypes caused by mutations in MECP2 and CDKL5, it has been suggested that the two genes play a role in common pathogenic processes. We show here that CDKL5 is a nuclear protein whose expression in the nervous system overlaps with that of MeCP2, during neural maturation and synaptogenesis. Importantly, we demonstrate that MeCP2 and CDKL5 interact both in vivo and in vitro and that CDKL5 is indeed a kinase, which is able to phosphorylate itself and to mediate MeCP2 phosphorylation, suggesting that they belong to the same molecular pathway. Furthermore, this paper contributes to the clarification of the phenotype associated with CDKL5 mutations and indicates that CDKL5 should be analyzed in each patient showing a clinical course similar to RTT but characterized by a lack of an early normal period due to the presence of seizures.
 ...
PMID:CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. 1591 71

Rett syndrome is a unique disorder mainly in girls characterized by global deceleration of psychomotor development and subsequent loss of acquired cognitive and motor skills, occurring after 6 to 18 months of apparently normal development. Previous study described that 26% of the cause of their death was sudden and unexpected. Although the cause of sudden death is still unknown, respiratory disorder, cardiac arrhythmia, and severe seizure might be related to sudden death. The possibility of sudden death should be informed to families of patients with Rett syndrome. Electrocardiogram should be examined in older patients, because prolongation of QTc and T wave abnormalities increase with advancing stage.
 ...
PMID:[Sudden death in Rett syndrome]. 1600 79

Children with an autism spectrum disorder (ASD) often are evaluated with electroencephalogram (EEG) studies to assess their risk for seizures or other underlying abnormalities. Their risk is estimated at 7% - 42%. EEG studies were conducted on a subgroup of children while following established practice parameters for evaluating children for ASD. Abnormal EEG results were obtained in 85 (27%) of the 316 children evaluatedfor ASD. Within the subset of abnormal results, 64 children had autism, 10 had an ASD or milder presentation, 6 had another developmental disorder, 3 had Rett syndrome, had Down syndrome, and 1 had Wolf-Hirshhorn syndrome. The abnormal EEG findings included epileptiform abnormalities in 55 patients (65%), and slowing in only 13 patients (15%). The focality of the epileptiformfindings included 26 (30%) in the temporal areas, 24 (28%) in the central area, 20 (23%) in the frontal area, and 7 (8%) in the occipital area. These findings confirm the importance of ongoing medicalfollow-up for children with ASDs, especially for those with abnormal EEG results.
 ...
PMID:Electroencephalogram abnormalities in children with autism spectrum disorders. 1600 17

Mutations in the CDKL5 gene (also known as STK9) have recently been shown to cause early onset epilepsy and severe mental retardation (ISSX or West syndrome). Patients with CDKL5 mutations sometimes also show features similar to those seen in Rett Syndrome (RTT). We have screened the CDKL5 gene in 94 patients with RTT or a RTT-like phenotype who had tested negative for MECP2 mutations (13 classical RTT female subjects, 25 atypical RTT female subjects, 40 RTT-like female and 16 RTT-like male subjects; 33 of the patients had early onset seizures). Novel pathogenic CDKL5 mutations were identified in three girls, two of whom had initially been diagnosed with the early onset seizure variant of RTT and the other with early onset seizures and some features of RTT. In addition, the 33 patients with early seizures were screened for the most common mutations in the ARX gene but none were found. Combining our three new cases with the previously published cases, 13/14 patients with CDKL5 mutations presented with seizures before the age of 3 months.
 ...
PMID:Early onset seizures and Rett-like features associated with mutations in CDKL5. 1601 84

We aimed to improve the understanding of genotype-phenotype correlations in Rett syndrome (RS) by adopting a novel approach to categorising phenotypic dimensions - separating typicality of presentation, outcome severity and age of onset - and by classifying MECP2 mutations strictly by predicted functional attributes. MECP2 mutation screening results were available on 190 patients with a clinical diagnosis of RS (140 cases with classic RS, 50 with atypical RS). 135 cases had identified mutations. Of the 140 patients, 116 with classic RS (82.9%) had an identified mutation compared with 19 of 50 patients (38%) with an atypical presentation. Cases with early onset of regression and seizures, and those with clinical features that might indicate alternative aetiologies, were less likely to have mutations. Individuals with late truncating mutations had a less typical presentation than cases with missense and early truncating mutations, presumably reflecting greater residual function of MECP2 protein. Individuals with early truncating mutations had a more severe outcome than cases with missense and late truncating mutations. These findings held when restricting the analysis to cases over 15 years of age and classic cases only. Previous findings of variation in severity among the common mutations were confirmed. The approach to phenotypic and genotypic classification adopted here allowed us to identify genotype-phenotype associations in RS that may aid our understanding of pathogenesis and also contribute to clinical knowledge on the impact of different types of mutations.
 ...
PMID:Dimensional phenotypic analysis and functional categorisation of mutations reveal novel genotype-phenotype associations in Rett syndrome. 1607 36

We describe a clinical profile of a male with Rett syndrome who presented initially with significant axial and peripheral hypotonia, head and truncal titubation and global delay. He is non-ambulatory, lost the few words he had learned and gradually developed hand stereotypes, breathing difficulties, seizures, scoliosis and has osteoporosis sleep problems and sludging in his gall bladder. Prior to diagnosis he underwent comprehensive neurological, metabolic and genetic investigations. After his older sister was diagnosed with atypical Rett syndrome; MECP2 mutation studies on him revealed a pathogenic mutation. His mother is a Rett carrier with a skewed inactivation of chromosome X. Clinical signs and symptoms required to meet the criteria for diagnosis of Rett syndrome have gradually evolved over time. This case demonstrates an unusual family history for Rett syndrome and alerts readers to the utility of screening males for Rett syndrome.
 ...
PMID:Clinical profile of a male with Rett syndrome. 1618 90

Rett syndrome is a leading cause of postnatal neurodevelopmental regression. Rett syndrome is caused by mutations in MECP2, the gene encoding methyl-CpG binding protein 2. In up to 96% of all classic cases, Rett syndrome cases are caused by mutations or deletions in MECP2. The phenotypic spectrum of MECP2 mutations is broad and includes mental retardation with or without seizures, Angelman syndrome-like phenotype, and autism. Mecp308/Y mice carry a truncating mutation and display many of the features seen in Rett syndrome. Social behavior abnormalities and impaired social interactions in Mecp308/Y mice suggest that MeCP2 plays a role in modulating the activity of genes and neurons important for social interactions. Mice that overexpress MeCP2 at twice the endogenous levels develop a progressive neurologic disorder, demonstrating that MeCP2 levels are tightly regulated and raising the possibility that duplications or gain-of-function mutations of MECP2 might underlie some cases of neurodevelopmental X-linked disorders.
 ...
PMID:MeCP2 dysfunction in humans and mice. 1622 28

Rett syndrome is a neurodevelopmental disorder that in most cases is consequent to a mutation in the MECP2 gene. The central nervous system is the primary organ system involved in Rett syndrome. Neurophysiologic evaluations provide information concerning the developmental aspects of Rett syndrome and the character and extent of involvement of the central, peripheral, and autonomic nervous system pathways. Evoked potentials typically demonstrate intactness of peripheral auditory and visual pathways and suggest dysfunction of central or "higher" cortical pathways. Somatosensory evoked potentials can be characterized by "giant" responses, suggesting cortical hyperexcitability. Cortical hyperexcitability is further suggested by the findings of the electroencephalogram (EEG), which are primarily characterized by a 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 Rett syndrome. However, many events presumed to be seizures have no EEG correlate during video-EEG monitoring. Impairment of the autonomic nervous system in Rett syndrome is suggested by an increased incidence of long Q-T intervals during electrocardiographic recordings and diminished heart rate variability. Autonomic nervous system dysfunction can contribute to the increased incidence of sudden unexpected death in Rett syndrome.
 ...
PMID:Neurophysiology of Rett syndrome. 1622 29


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