Febrile seizures and genetic epilepsy with febrile seizuresplus(GEFS+)

Abstract

Aim. To review the literature about febrile seizures and GEFS plus with special emphasis on management and outcome. Methods. Selected literature review. Results. Febrile seizures are the most common convulsive event in humans, occurring in 2-6% of the population. The aetiology is complex with strong evidence for a heterogeneous genetic predisposition interacting with fever of any cause, with certain viral infections having a greater effect. A large amount of literature has established that febrile seizures have no long-term consequences on cognition or behaviour. Unfortunately, about 40% of children with a first febrile seizure will have a recurrence. The strongest predictor of recurrence is age <14-16 months at the time of the first febrile seizure. Epilepsy follows febrile seizures in ∼3% cases, with the concepts of simple and complex febrile seizures providing relatively weak prediction. Very prolonged febrile seizures may lead to mesial temporal sclerosis and temporal lobe epilepsy although the degree of risk remains uncertain. Investigations beyond establishing the cause of the provoking fever are nearly always unnecessary.

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

“…Our findings also support that the genetic susceptibility for epilepsy is shared among different races. While the clinical presentations for these patients carrying the recurrent mutations are similar to the Caucasian children based on the review of the data available in the reports1415162627. It would be interesting in future study to compare them systematically in parallel with larger sample size and determine whether a significant modifier effect may be present in different genetic background.…”

“…These variants are either recurrent mutations or novel but deleterious variants in known epilepsy genes. We identified 2 recurrent mutations (c.311 C>T, p.Ala104Val and c.181 C>T, p.Leu61Phe) in SCN1A gene (http://www.ncbi.nlm.nih.gov/clinvar), a known epilepsy gene for Dravet syndrome (DS), generalized epilepsy with febrile seizures plus (GEFS+) and epileptic encephalopathy141516. In D1353 family, a de novo but recurrent mutation of c.311 C>T was found in a boy with Dravet syndrome, intractable seizure, significant regression of intellectual ability, and autistic behaviors.…”

“…The interesting question is whether the variants in these genes may function as a modifier to contribute to the clinical phenotypes caused by the mutations in SCN1A . The extreme variable expressivity is well documented for individual with SCN1A mutation141516. However, little is known about the underlying molecular mechanism contributing to the variable expressivity associated with SCN1A mutations.…”

The role of EEG in the diagnosis and classification of the epilepsy syndromes: a tool for clinical practice by the ILAE Neurophysiology Task Force (Part 2)

“…The term "generalised epilepsy with febrile seizure plus" (Scheffer and Berkovic, 1997) has been renamed "genetic epilepsy with febrile seizure plus" because it is now recognised that some of the associated epilepsies may be focal (Camfield and Camfield, 2015;Zhang et al, 2017). The term "generalised epilepsy with febrile seizure plus" (Scheffer and Berkovic, 1997) has been renamed "genetic epilepsy with febrile seizure plus" because it is now recognised that some of the associated epilepsies may be focal (Camfield and Camfield, 2015;Zhang et al, 2017).…”

Large-scale structural alteration of brain in epileptic children with SCN1A mutation

“…The spectrum of epilepsy related to SCN1A mutation spans from milder phenotypes, such as genetic epilepsy with febrile seizures plus (GEFS +), to severe myoclonic epilepsy of infancy (SMEI), also known as Dravet syndrome (Gambardella and Marini, 2009). GEFS + is characterized by recurrent febrile seizure events beyond 5–6 years of age, even up to the teenage years, and can develop a number of afebrile heterogeneous seizure types with remission in adolescence (Scheffer and Berkovic, 1997, Camfield and Camfield, 2015). Dravet syndrome is a deleterious forms of childhood epilepsy characterized by recurrent febrile and afebrile seizures in the first year, followed by multiple seizure types resistant to various antiepileptic drugs, as well as cognitive, behavioral, and motor impairment (Dravet, 2011).…”