Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009952 (febrile convulsions)
 1,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome characterized by heterogeneous phenotypes ranging from mild disorders such as febrile seizures to epileptic encephalopathies (EEs) such as Dravet syndrome (DS). Although DS often occurs with de novo SCN1A pathogenic variants, milder GEFS+ spectrum phenotypes are associated with inherited pathogenic variants. We identified seven cases with non-EE GEFS+ phenotypes and de novo SCN1A pathogenic variants, including a monozygotic twin pair. Febrile seizures plus (FS+) occurred in six patients, five of whom had additional seizure types. The remaining case had childhood-onset temporal lobe epilepsy without known febrile seizures. Although early development was normal in all individuals, three later had learning difficulties, and the twin girls had language impairment and working memory deficits. All cases had SCN1A missense pathogenic variants that were not found in either parent. One pathogenic variant had been reported previously in a case of DS, and the remainder were novel. Our finding of de novo pathogenic variants in mild phenotypes within the GEFS+ spectrum shows that mild GEFS+ is not always inherited. SCN1A screening should be considered in patients with GEFS+ phenotypes because identification of pathogenic variants will influence antiepileptic therapy, and prognostic and genetic counseling.
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PMID:De novo SCN1A pathogenic variants in the GEFS+ spectrum: Not always a familial syndrome. 2808 35

Epilepsy is a common chronic neurological disease affecting almost 3 million people in the United States and 50 million people worldwide. Despite availability of more than two dozen FDA-approved anti-epileptic drugs (AEDs), one-third of patients fail to receive adequate seizure control. Specifically, pediatric genetic epilepsies are often the most severe, debilitating and pharmaco-resistant forms of epilepsy. Epileptic syndromes share a common symptom of unprovoked seizures. While some epilepsies/forms of epilepsy are the result of acquired insults such as head trauma, febrile seizure, or viral infection, others have a genetic basis. The discovery of epilepsy associated genes suggests varied underlying pathologies and opens the door for development of new "personalized" treatment options for each genetic epilepsy. Among these, Dravet syndrome (DS) has received substantial attention for both the pre-clinical and early clinical development of novel therapeutics. Despite these advances, there is no FDA-approved treatment for DS. Over 80% of patients diagnosed with DS carry a de novo mutation within the voltage-gated sodium channel gene SCN1A and these patients suffer with drug resistant and life-threatening seizures. Here we will review the preclinical animal models for DS featuring inactivation of SCN1A (including zebrafish and mice) with an emphasis on seizure phenotypes and behavioral comorbidities. Because many drugs fail somewhere between initial preclinical discovery and clinical trials, it is equally important that we understand how these models respond to known AEDs. As such, we will also review the available literature and recent drug screening efforts using these models with a focus on assay protocols and predictive pharmacological profiles. Validation of these preclinical models is a critical step in our efforts to efficiently discover new therapies for these patients. The behavioral and electrophysiological drug screening assays in zebrafish will be discussed in detail including specific examples from our laboratory using a zebrafish scn1 mutant and a summary of the nearly 3000 drugs screened to date. As the discovery and development phase rapidly moves from the lab-to-the-clinic for DS, it is hoped that this preclinical strategy offers a platform for how to approach any genetic epilepsy.
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PMID:Preclinical Animal Models for Dravet Syndrome: Seizure Phenotypes, Comorbidities and Drug Screening. 2991 37

Patients with temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS) are eligible candidates for resective epilepsy surgery. We report on 2 male patients aged 4 years with suspected TLE due to MTS who were referred for presurgical evaluation. Both patients came to medical attention within the first year of life suffering from febrile status epileptici and subsequent unprovoked seizures. The following years, moderate developmental delay was present. High-resolution magnetic resonance imaging confirmed hippocampal sclerosis. Continuous EEG video monitoring revealed seizure patterns contralateral to the MTS in both patients. Genetic analysis was performed as both the clinical presentation of the patients and EEG video monitoring findings were not consistent with the presence of the hippocampal sclerosis alone and revealed de novo mutations within exon of the SCN1A gene. Resective surgical strategies were omitted due to the genetic findings. In conclusion, both patients suffered from a dual pathology syndrome with ( a) TLE related to MTS resulting most likely from recurrent febrile status in early childhood and ( b) Dravet syndrome, which is most likely the cause of the febrile convulsions leading to the MTS in these 2 patients.
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PMID:Mesial Temporal Sclerosis in SCN1A-Related Epilepsy: Two Long-Term EEG Case Studies. 3011 35


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