GEFS Research Articles

Research progress in genetic studies of genetic epilepsy with febrile seizures plus

Genetic epilepsy with febrile seizures plus(GEFS+ ) is a genetically related epilepsy syndrome, characterized by a distinctive pattern of phenotypic heterogeneity and genetic heterogeneity.An increasing number of studies illustrate that a variety of pathogenic variations participate in the pathogenesis of GEFS+ , but the pathogenesis and genetic mechanisms are not fully understood, and most families can not find pathogenic genes.With the improvement of genetic techniques, the pathogenesis of GEFS+ will be better explained and a new basis will be provided for its diagnosis and precision treatment.This article discusses the clinical manifestation, genetic research, diagnosis and treatment of GEFS+ , aiming at raising awareness of the disease. Key words: Genetic epilepsy with febrile seizures plus; Hereditary; Clinical manifestation; Diagnosis; Treatment

The relationship between vaccination and febrile seizure、GEFS+ and Dravet syndrome

Vaccination in children suffering neurological diseases is a troublesome issue that people especially pediatricians are reluctant to mention.Due to worrying about the emergence of adverse reactions and concerning on the heat induced seizure, doctors and parents tend to cancel or do not recommend these children to be vaccinated.Additionally, the heat sensitive seizures, such as febrile seizure(FS), generalized epilepsy with febrile seizure plus(GEFS+ ), Dravet syndrome account for the largest proportion of the seizure related disease and epilepsy syndrome.Their pathogenesis has been proved relating to the mutation of SCN gene of the sodium channel.For children with FS, GEFS+ , and Dravet syndrome, vaccination may lead to fever, which even may bring about convulsions, but it will not result in worse prognosis. Key words: Febrile seizure; GEFS+; Dravet syndrome; Vaccination

Fgf13 Identified as a Novel Cause of GEFS.

Fgf13 Identified as a Novel Cause of GEFS.

Mutational analysis of SCN1A gene in Chinese families with generalized epilepsy with febrile seizures plus

Objective To investigate the gene mutations of SCN1A in the families with generalized epilepsy with febrile seizures plus (GEFS+ ) and analyze the genotype-phenotype correlations in GEFS+ families. Methods Genomic DNA was extracted from peripheral blood lymphocytes of the probands and other available members in the GEFS+ families.The phenotypes of the affected members were analyzed.The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing. Results Two in 17 families(11.76%) were found with novel SCN1A mutations(C142T, S573R), presenting heterozygote missense mutations in exon 3 and exon 11 located in highly conserved region.The above 2 mutations had not been reported.The proband and other affected members in pedigree 1 all carried the mutation(C142T). Their clinical phenotype included febrile seizures(FS) and FS plus(FS+ ) with generalized tonic-clonic seizures and the penetrance rate was about 75.0%(3/4 cases). The phenotype of the proband in pedigree 2 harbored S573R were FS+ with partial seizures and the penetrance rate was about 66.7%(2/3 cases). Conclusions Two novel missense mutations were identified in the GEFS+ families, which were consistent with autosomal dominant inheritance with incomplete penetrance.C142T located in the S6 transmembrane regions at domain D1 and S573R located between S5-S6 segment at domain D4 in the voltage-gated sodium channel.Two families harbored different genetic mutations, in which the affected members had different clinical phenotypes.SCN1A is one of the pathogenic gene in Chinese GEFS+ patients and the genotypes of GEFS+ family is associated with the clinical phenotypes. Key words: Generalized epilepsy with febrile seizures plus; SCN1A gene; Mutation

Phenotype and SCN1A gene mutation screening in 39 families with generalized epilepsy with febrile seizures plus

To summarize the phenotypes and identify SCN1A mutations in families with generalized epilepsy with febrile seizures plus (GEFS(+)), and analyze the genotype- phenotype correlations in GEFS(+) families. Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS(+) families. The phenotypes of the affected members were analyzed. The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing. In 39 GEFS(+) families, there were 196 affected members, ranging from 2 to 22 affected members in each family. Their phenotypes included febrile seizures (FS) in 92(46.9%), febrile seizures plus (FS(+)) in 62(31.6%), FS or FS(+) with partial seizures in 12(6.1%), afebrile generalized tonic-clonic seizures (AGTCS) in 11(5.6%), myoclonic atonic epilepsy in 8(4.1%), Dravet syndrome in 2(1.0%), childhood absence epilepsy in 1 (0.5%), FS(+) with myoclonic seizures in 1(0.5%), AGTCS and myoclonic seizures in 1 (0.5%), partial seizures in 1 (0.5%), unclassified seizures in 5 (2.6%). Four families were found with SCN1A mutations, including three families with missense mutation (N935H, R101Q, G1382R) and one family with truncation mutation (C373fsx378). In three families with missense mutations, the phenotypes include FS, FS(+), FS(+) with partial seizures, and AGTCS. In one family with truncation mutation, the phenotypes included FS, FS(+), and Dravet syndrome. The mother of proband in the family with missense mutation (R101Q) and the father of proband in the family with truncation mutation (C373fsx378) were both somatic mosaicism. Both of their phenotypes were FS(+). The most common phenotypes of GEFS(+) were FS and FS(+), followed by the FS/FS(+) with partial seizures and AGTCS. The most severe phenotype was Dravet syndrome. SCN1A mutation rate in GEFS(+) was about 10%. Missense mutation was common in GEFS(+) families, few with truncation mutation. Few members of GEFS(+) families had somatic mosaicism of SCN1A mutations and their phenotypes were relatively mild.

Current Proceedings of Febrile Seizures and Related Epileptic Syndromes in CN1A: From Bedside to Bench

Febrile seizures (FS) characterize the majority of childhood seizures, it is well recognized highly inheritance in family of children with FS. Several genetic loci related to FS had been defined imply the genetic heterogeneity of FS. Nevertheless, molecular genetic approaches toward understanding FS related epilepsies have been explored this decade; especially sodium channel mutation 1α (SCN1A). Among them, generalized epilepsy with FS plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) are highlighted. This review demonstrates recent development from clinics to genetics of FS and the update of genetics in FS associated epilepsy in SCN1A mutation and related epileptic syndromes.

SCN1A in SMEI, ICEGTC, and GEFS+: Alphabet Soup or Emerging Genotypic-Phenotypic Clarity?

SCN1A in SMEI, ICEGTC, and GEFS+: Alphabet Soup or Emerging Genotypic-Phenotypic Clarity?