Dravet syndrome: A study of 53 patients
TL;DR: The present study confirms the severity and intractability of the seizures and the difficulties to make an early diagnosis in Dravet syndrome.
About: This article is published in Epilepsy Research.The article was published on 2006-08-01. It has received 86 citations till now. The article focuses on the topics: Dravet syndrome & Epilepsy.
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TL;DR: An exhaustive review of the clinical genetics and research genetics literature in an attempt to collate all genes and recurrent genomic imbalances that have been implicated in the etiology of ASD shows that autism is not a single clinical entity but a behavioral manifestation of tens or perhaps hundreds of genetic and genomic disorders.
851 citations
TL;DR: Clinical manifestations at the onset, at the steady state, and during the course of the disease are analyzed in detail for the typical Dravet syndrome, and the differential diagnosis is discussed.
Abstract: Dravet syndrome was described in 1978 by Dravet (1978) under the name of severe myoclonic epilepsy in infancy (SMEI). The characteristics of the syndrome were confirmed and further delineated by other authors over the years. According to the semiologic features, two forms have been individualized: (1) the typical, core, SMEI; and (2) the borderline form, SMEIB, in which the myoclonic component is absent or subtle. Clinical manifestations at the onset, at the steady state, and during the course of the disease are analyzed in detail for the typical Dravet syndrome, and the differential diagnosis is discussed. Onset in the first year of life by febrile or afebrile clonic and tonic-clonic, generalized, and unilateral seizures, often prolonged, in an apparently normal infant is the first symptom, suggesting the diagnosis. Later on, multiple seizure types, mainly myoclonic, atypical absences, and focal seizures appear, as well as a slowing of developmental and cognitive skills, and the appearance of behavioral disorders. Mutation screening for the SCN1A gene confirms the diagnosis in 70-80% of patients. All seizure types are pharmacoresistent, but a trend toward less severe epilepsy and cognitive impairment is usually observed after the age of 5 years.
451 citations
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...Surprisingly, obtundation statuses were not reported in the two recent studies (Caraballo & Fejerman, 2006; Ragona et al., 2010)....
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TL;DR: This critical analysis of the ketogenic diet should provide the impetus for further clinical and basic research into the diet's application and mechanisms of action.
Abstract: The ketogenic diet remains a valuable therapeutic option for patients with intractable epilepsy. Clinical aspects of the diet's success may provide insights into epileptogenesis and anticonvulsant action. The diet's efficacy has been established primarily through large case series. The diet has been used successfully in patients with many different epilepsy syndromes in countries around the world. Potential adverse effects can be avoided with careful attention during the diet's initiation and maintenance phases. In the last decade, variations to the classical ketogenic diet have been utilized. Ketogenic diets now are being used for diseases other than epilepsy. This critical analysis of the diet should provide the impetus for further clinical and basic research into the diet's application and mechanisms of action.
208 citations
TL;DR: The whole clinical course of Dravet syndrome comprehensively, from infancy through adulthood, is elucidated comprehensively for the first time.
Abstract: Summary
Purpose: We intended to elucidate the whole clinical course of Dravet syndrome (DS) comprehensively, from infancy through adulthood.
Methods: Subjects were 31 patients with DS (14 with typical DS, and 17 with borderline DS) who were followed from childhood to at least 18 years of age. Their seizures, abilities, and electroencephalography (EEG) findings were investigated and statistically analyzed.
Results: The clinical findings of the patients with typical DS and those with borderline DS became largely similar in adolescence and adulthood. Seizures were intractable in childhood in all patients, but suppressed in five (16.1%) during follow-up. Thirty-five (87.5%) of the 40 apparently generalized convulsive seizures that were captured by ictal EEG recording at 7 years of age or later were of focal origin. The seizure-free outcomes were significantly correlated with the experience of <3 episodes of convulsive status epilepticus, and also with disappearance of spikes on the follow-up EEGs. Mental outcomes involving less severe intellectual disability were correlated with the presence of occipital alpha rhythms in the background activity of the follow-up EEGs. Mean age at the recording of the follow-up EEGs was 23.8 years.
Discussion: Prevention of the occurrence of convulsive status epilepticus was indicated to be critically important for the improvement of seizure prognosis in DS.
167 citations
Cites background from "Dravet syndrome: A study of 53 pati..."
...…follow-up studies of DS (Fujiwara et al., 1987; Sugama et al., 1987; Ohtsuka et al., 1991; Fujiwara et al., 1992; Maniwa, 1993; Ohki et al., 1997; Caraballo & Fejerman, 2006), but few of these describe the clinical features of DS in adulthood (Rossi et al., 1991; Oguni et al., 2001; Jansen et…...
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TL;DR: interpretation of the significance of a SCN1A missense mutation requires a thorough understanding of the phenotypes in the GEFS+ spectrum whereas a de novo truncation mutation is likely to be associated with a severe phenotype.
Abstract: Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) can both arise due to mutations of SCN1A, the gene encoding the alpha 1 pore-forming subunit of the sodium channel GEFS+ refers to a familial epilepsy syndrome where at least two family members have phenotypes that fit within the GEFS+ spectrum The GEFS+ spectrum comprises a range of mild to severe phenotypes varying from classical febrile seizures to Dravet syndrome Dravet syndrome is a severe infantile onset epilepsy syndrome with multiple seizure types, developmental slowing and poor outcome More than 70% of patients with Dravet syndrome have mutations of SCN1A; these include both truncation and missense mutations In contrast, only 10% of GEFS+ families have SCN1A mutations and these comprise missense mutations GEFS+ has also been associated with mutations of genes encoding the sodium channel beta 1 subunit, SCN1B, and the GABA(A) receptor gamma 2 subunit, GABRG2 The phenotypic heterogeneity that is characteristic of GEFS+ families is likely to be due to modifier genes Interpretation of the significance of a SCN1A missense mutation requires a thorough understanding of the phenotypes in the GEFS+ spectrum whereas a de novo truncation mutation is likely to be associated with a severe phenotype Early recognition of Dravet syndrome is important as aggressive control of seizures may improve developmental outcome
154 citations
Cites background from "Dravet syndrome: A study of 53 pati..."
...The ketogenic diet can also be effective and deserves consideration [55,56]....
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References
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TL;DR: A diagnostic scheme that makes use of standardized terminology and concepts to describe individual patients is proposed, and a variety of approaches to classification are possible, and some are presented here by way of example only.
Abstract: The International League Against Epilepsy (ILAE) made a major contribution when it established standardized classifications and terminology for epileptic seizures and syndromes. This provided a universal vocabulary that not only facilitated communication among clinicians, but also established a taxonomic foundation for performing quantitative clinical and basic research on epilepsy. Much, however, has changed since the adoption of the currently used Classification of Epileptic Seizures in 1981 (1) and the Classification of Epilepsies and Epileptic Syndromes in 1989 (2). Consequently, the Executive Committee of the ILAE, which took office in July 1997, agreed that review and revision of the current classification system would be a priority for this Executive term. A Task Force on Classification and Terminology was appointed, which divided itself into four working groups concerned with Descriptive Terminology for Ictal Events; Seizures; Syndromes and Diseases; and Impairment. During the course of several meetings and vigorous e-mail discussions, the Task Force agreed that it would not be possible to replace the current international classifications with similar revised and updated classifications that would be universally accepted and meet all the clinical and research needs such a formal organizational system would be expected to provide. Rather, the Task Force is proposing a diagnostic scheme that makes use of standardized terminology and concepts to describe individual patients (Table 1). Within this diagnostic scheme, a variety of approaches to classification are possible, and some are presented here by way of example only. The Task Force views the development of specific classifications as a continuing work in progress. Flexible and dynamic classifications will be revised periodically based not only on rapidly emerging new information, but also on the resolution of problems that will inevitably be identified through use. At this point, the proposal does include several definitive changes in concepts and terminology (Table 2), and classifications are presented as examples of what could be devised in the future.
2,106 citations
TL;DR: Missense mutations in the gene that codes for a neuronal voltage-gated sodium-channel alpha-subunit (SCN1A) were identified in families with generalized epilepsy with febrile seizures plus (GEFS+) and seven unrelated patients with SMEI were screened for mutations.
Abstract: Severe myoclonic epilepsy of infancy (SMEI) is a rare disorder that occurs in isolated patients. The disease is characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, andsimple and complex partial seizures. Psychomotor development stagnates around the second year of life. Missense mutations in the gene that codes for a neuronal voltage-gated sodium-channel α-subunit (SCN1A) were identified in families with generalized epilepsy with febrile seizures plus (GEFS+). GEFS+ is a mild type of epilepsy associated with febrile and afebrile seizures. Because both GEFS+ and SMEI involve fever-associated seizures, we screened seven unrelated patients with SMEI for mutations in SCN1A. We identified a mutation in each patient: four had frameshift mutations, one had a nonsense mutation, one had a splice-donor mutation, and one had a missense mutation. All mutations are de novo mutations and were not observed in 184 control chromosomes.
1,115 citations
Book•
05 Dec 2005
TL;DR: Classifications: evolving concepts Genetic bases of epileptic syndromes EEG traits of epilepsies Syndrome & brain development Syndromes & prognosis Syndroms & antiepileptic drugs
Abstract: Classifications: evolving concepts Genetic bases of epileptic syndromes EEG traits of epileptic syndromes Syndromes & brain development Syndromes & prognosis Syndromes & antiepileptic drugs Benign neonatal seizures & epilepsies Early severe neonatal & infantile epilepsies Infantile spasms Idiopathic focal epilepsies in infants Dravet syndrome Idiopathic myoclonic epilepsies in infancy & early childhood Febrile seizures & GEFS+ The Lennox-Gastaut syndrome Idiopathic focal epilepsies in childhood CSWS & related syndromes Childhood absence epilepsy Myoclonic absences & absences with myoclonias Juvenile myoclonic epilepsies Juvenile absence epilepsy IGE with Grand Mal seizures only Genetically determined focal epilepsies Rasmussens syndrome Temporal lobe epilepsy syndromes Frontal lobe epilepsy syndromes Syndromes in the elderly Myoclonic status in fixed encephalopathies Epilepsy in inborn errors of metabolism Non-idiopathic focal epilepsies in childhood Photosensitivity & syndromes Complex & other reflex epilepsies Epilepsy & chromosomal disorders Progressive myoclonus epilepsies Epilepsy & cortical malformations Isolated focal seizures in adolescence.
972 citations
Book•
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TL;DR: Treatment and quality of life have improved because the syndrome-specific efficacy profile of drugs is better known, and there is heightened awareness that compounds with severe cognitive side-effects and heavy polytherapies should be avoided.
Abstract: 10·5 million children worldwide are estimated to have active epilepsy. Over the past 15 years, syndrome-oriented clinical and EEG diagnosis, and better aetiological diagnosis, especially supported by neuroimaging, has helped to clarify the diversity of epilepsy in children, and has improved management. Perinatal and postinfective encephalopathy, cortical dysplasia, and hippocampal sclerosis account for the most severe symptomatic epilepsies. Ion channel defects can underlie both benign age-related disorders and severe epileptic encephalopathies with a progressive disturbance in cerebral function. However, the reasons for age-related expression in children are not understood. Neither are the mechanisms whereby an epileptic encephalopathy originates. Several new drugs have been recently introduced but have provided limited therapeutic benefits. However, treatment and quality of life have improved because the syndrome-specific efficacy profile of drugs is better known, and there is heightened awareness that compounds with severe cognitive side-effects and heavy polytherapies should be avoided. Epilepsy surgery is an important option for a few well-selected individuals, but should be considered with great caution when there is no apparent underlying brain lesion.
740 citations
TL;DR: A genetic epilepsy syndrome termed generalized epilepsy with febrile seizures plus (GEFS+) is identified, which explains the epilepsy phenotypes of previously poorly understood benign childhood generalized epilepsies.
Abstract: The clinical and genetic relationships of febrile seizures and the generalized epilepsies are poorly understood. We ascertained a family with genealogical information in 2000 individuals where there was an unusual concentration of individuals with febrile seizures and generalized epilepsy in one part of the pedigree. We first clarified complex consanguineous relationships in earlier generations and then systematically studied the epilepsy phenotypes in affected individuals. In one branch (core family) 25 individuals over four generations were affected. The commonest phenotype, denoted as 'febrile seizures plus' (FS+), comprised childhood onset (median 1 year) of multiple febrile seizures, but unlike the typical febrile convulsion syndrome, attacks with fever continued beyond 6 years, or afebrile seizures occurred. Seizures usually ceased by mid childhood (median 11 years). Other phenotypes included FS+ and absences, FS+ and myoclonic seizures, FS+ and atonic seizures, and the most severely affected individual had myoclonic-astatic epilepsy (MAE). The pattern of inheritance was autosomal dominant. The large variation in generalized epilepsy phenotypes was not explained by acquired factors. Analysis of this large family and critical review of the literature led to the concept of a genetic epilepsy syndrome termed generalized epilepsy with febrile seizures plus (GEFS+). GEFS+ has a spectrum of phenotypes including febrile seizures, FS+ and the less common MAE. Recognition of GEFS+ explains the epilepsy phenotypes of previously poorly understood benign childhood generalized epilepsies. In individual patients the inherited nature of GEFS+ may be overlooked. Molecular genetic study of such large families should allow identification of genes relevant to febrile seizures and generalized epilepsies.
704 citations