The relationship between vaccination and febrile seizure、GEFS+ and Dravet syndrome / 国际儿科学杂志

Vaccination in children suffering neurological diseases is a troublesome issue that people es-pecially 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 fe-brile 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.

Brain-derived Neurotrophic Factor(BDNF) SNP 6265 Polymorphisms in Febrile Seizure and GEFS+ / 대한소아신경학회지

PURPOSE: Febrile seizure(FS) is one of the most common neurological conditions during childhood, but the pathogenesis of FS remains ambiguous. Various studies have shown that brain-derived neurotrophic factor(BDNF) increased neuronal excitability. In this study, to determine whether the polymorphisms of SNP 6265 within the gene encoding BDNF are associated with susceptibility to FS, the frequencies of the polymorphisms were investigated in children with FS and control subjects. In addition, we analyzed the SNP 6265 polymorphisms in Generalized epilepsy with febrile seizures plus (GEFS+) that hasn't been studied as yet in Korea. METHODS: A total of 79 children selected throughout a collaborative study of Catholic Child Neurology Research Group were divided into three groups: (1) FS(n=30); (2) GEFS+ (n=19); (3) control subjects(n=30). Genotypes and allelic frequencies for the polymorphisms of SNP 6265 located at nucleotide 196 was analyzed and compared among the groups. RESULTS: In this study, proportions for A homozygote, A/G heterozygote and G homozygote for BDNF were as follows: in FS, 46.7%, 36.7% and 16.7%, in GEFS+, 26.3%, 47.4% and 26.3% and in control subjects, 60.0%, 16.7% and 23.3%. The allele A and G frequencies for BDNF in FS were 65.0% and 35.0%, in GEFS+ were 50% and 50%, and in control subjects were 68.3% and 31.7%. However, these differences in genotype proportions and allele frequencies among three groups were not significant. CONCLUSION: These results suggest that genomic variations of BDNF might not be the susceptibility factor for FS and GEFS+ in Korean population.

Clinical Features of GEFS+ and its Neurological Outcome / 대한소아신경학회지

PURPOSE:The aim of this study was to characterize the clinical and electroencephalographic features as well as the neurologic outcomes of GEFS+(Genenralized Epilepsy with Febrile Seizures Plus). METHODS:We evaluated 55 children with GEFS+ who admitted at the Department of Peditrics, Kangnam Sacred Heart Hospital from 1993 to 2004. We formed them into two groups by age of first febrile seizure; Group A( or = 6 years). We analyzed the clinical features, electroencephalographic findings and the neurological outcomes of the subjects. RESULTS:The mean age of the initial febrile seizures of 55 subjects was 3 years and 9 months. 41 subjects had their initial febrile seizures under 6 years of age while 14 subjects after 6 years of age. 17 subjects had family history of seizures. The mean frequency of seizure is 4.4 times and the types of convulsions were mainly generalized. Nineteen(37.3%) showed abnormal finding on EEG and twenty three(41%) were treated with antiepileptic drug(AED) for long-term prophylaxis. Never the less, there was no subject with abnormalities in the neurological outcomes. The group with the initial seizures occurred under 6 years of age had more family history of seizures, higher frequency of total seizures, febrile seizures, and was administered with AEDs longer than the other group. CONCLUSION:In our study of GEFS+, the clinical features and the results of the electroencephalograms were various. While there were cases with a need of long term administration of AEDs, few cases of neurological abnormalities or developmental delay were seen. The group of the initial febrile seizures under 6 years of age revealed more family history of seizures, higher frequency of seizures than the other group.

Interleukin-1beta Promoter Polymorphisms in Febrile Seizures and GEFS+ / 대한소아신경학회지

PURPOSE: Studies gave conflicting results as to the association between febrile seizures(FSs) and IL1B promoter polymorphisms. In the present study, to determine whether or not the function-related two single nucleotide base C/T biallelic polymorphisms in the promoter region at positions -31 and -511 of the IL1B gene are associated with susceptibility to FSs, the frequencies of the polymorphisms were investigated in children with FSs and GEFS+, and normal control subjects. METHODS: 72 FSs, 23 GEFS+ and 174 healthy control subjects were selected throughout a collaborative study of Catholic Child Neurology Research Group. IL1B promoter -31 C/T and -511 C/T genotyping was performed by means of PCR-restriction fragment length polymorphism. RESULTS: The distribution of IL1B -31 genotypes and the frequencies of allele in children with FSs and GEFS+, and healthy control subjects were not significantly different. The distributions of IL1B -31 genotypes(CC, CT, TT) are 22.2%, 50%, and 27.8% in children with FSs, 21.7%, 43.5% and 34.8% in children with GEFS+, and 27.6%, 49.3% and 24.1% in healthy control subjects. The distribution of IL1B -511 genotypes and the frequencies of allele in children with FSs and GEFS+, and healthy control subjects were not significantly different. The distributions of IL1B -511 genotypes(CC, CT, TT) are 23.6%, 47.2%, and 29.2% in children with FSs, 26.1%, 39.1% and 34.8% in children with GEFS+, and 27.6%, 49.3% and 24.1% in healthy control subjects. CONCLUSION: Theses data suggest that genomic variations of IL1B promoter might not be one of the susceptibility factors for FSs in the Korean population.

Single Nucleotide Polymorphisms of GABRG2 in Febrile Seizures and GEFS+ / 대한소아신경학회지

PURPOSE: Febrile seizures are characterized by a heterogenous phenotype segregating as an autosomal dominant trait with incomplete penetrance. Mutations in GABRG2 gene were identified in two families with generalized epilepsy and febrile seizures plus (GEFS+) and with absence epilepsy and febrile seizures(FSs). The present study assessed the role of GABRG2 gene in FSs and GEFS+ of the Korean population. METHODS: 66 FSs, 20 GEFS+ and 94 healthy control subjects were selected throughout a collaborative study of Catholic Child Neurology Research Group. The SNP211037 of GABRG2 was screened by DHPLC. DNA fragments showing variant chromatograms were subsequently sequenced. Genotypes and allelic frequencies for GABRG2 gene polymorphism in three groups were compared. RESULTS: The number of individuals with the GABRG2(SNP211037)-C/C genotype in patients with FSs was significantly greater compared with that in healthy control subjects and the GABRG2(SNP211037)-C allele frequency in patients with FSs was significantly higher than that in healthy control subjects. The odds ratio for developing FSs in individuals with the GABRG2(SNP211037)-CC genotype was 5.96 compard with individuals with the GABRG2(SNP211037)-T/T genotype. In contrast, the GABRG2 (SNP211037) gene in GEFS+ and control groups was not significantly different. CONCLUSION: Theses data suggest that genomic variations of GABRG2 might be one of the susceptibility factors for FSs in the Korean population.

Single Nucleotide Polymorphisms of SCN1A-exon 9 in GEFS+ / 대한소아신경학회지

PURPOSE: Febrile seizures affect 2-5% of all children younger than 6 years old. A small proportion of children with febrile seizures later develop epilepsy. Muations in the voltage-gated sodium channel subunit gene SCN1A have been associated with febrile seizures(FSs) in autosomal dominant generalized epilepsy with febrile seizures plus (GEFS+) families and severe myoclonic epilepsy of infancy. The present study assessed the role of SCN1A in familial typical FSs. METHODS: 22 GEFS+ and 62 FSs were selected throughout a collaborative study of Catholic Child Neurology Research Group. The exon 9 region of SCN1A was screened by DHPLC. DNA fragments showing variant chromatograms were subsequently sequenced. RESULTS: A total 84 individuals(22 GEFS+ and 62 FSs) was screened for mutations. Among 22 GEFS+ and 62 FSs patients, five and forty nine showed simple FSs, and seventeen and thirteen had complex FSs. 0% and 8.3% were younger than 12 months old, 22.7% and 46.8% were between 12 and 35 months old, 18.2% and 41.9% were between 36 and 83 months old, and 59.1% and 0% were older than 84 months old. The ratios of male to female were 1.75:1 and 1.82:1. Mutational analysis detected no mutation of SCN1A. Mutational analysis detected eleven silent exonic polymorphisms at G1212A in exon 9 and forty two polymorphisms on intron 9, and 23 intron A/As in 73 homozygote samples. There were no significant differences in allelic frequencies(G/G intron A/A or G/G, G/G intron G/A, G/A intron G/A, reported G/A) of G1212A in SCN1A-exon 9 between the patients with GEFS+ and FSs(31.8% vs. 32.3%, 54.5% vs. 54.8%, 9% vs. 6.5%, 4.5% vs. 6.5%). CONCLUSION: Although our study demonstrated that SCN1A is not frequently involved in GEFS+ and FSs, further systemic research would be necessary.

Single Nucleotide Polymorphisms of SCN1A-exon 9 in GEFS+ / 대한소아신경학회지

PURPOSE: Febrile seizures affect 2-5% of all children younger than 6 years old. A small proportion of children with febrile seizures later develop epilepsy. Muations in the voltage-gated sodium channel subunit gene SCN1A have been associated with febrile seizures(FSs) in autosomal dominant generalized epilepsy with febrile seizures plus (GEFS+) families and severe myoclonic epilepsy of infancy. The present study assessed the role of SCN1A in familial typical FSs. METHODS: 22 GEFS+ and 62 FSs were selected throughout a collaborative study of Catholic Child Neurology Research Group. The exon 9 region of SCN1A was screened by DHPLC. DNA fragments showing variant chromatograms were subsequently sequenced. RESULTS: A total 84 individuals(22 GEFS+ and 62 FSs) was screened for mutations. Among 22 GEFS+ and 62 FSs patients, five and forty nine showed simple FSs, and seventeen and thirteen had complex FSs. 0% and 8.3% were younger than 12 months old, 22.7% and 46.8% were between 12 and 35 months old, 18.2% and 41.9% were between 36 and 83 months old, and 59.1% and 0% were older than 84 months old. The ratios of male to female were 1.75:1 and 1.82:1. Mutational analysis detected no mutation of SCN1A. Mutational analysis detected eleven silent exonic polymorphisms at G1212A in exon 9 and forty two polymorphisms on intron 9, and 23 intron A/As in 73 homozygote samples. There were no significant differences in allelic frequencies(G/G intron A/A or G/G, G/G intron G/A, G/A intron G/A, reported G/A) of G1212A in SCN1A-exon 9 between the patients with GEFS+ and FSs(31.8% vs. 32.3%, 54.5% vs. 54.8%, 9% vs. 6.5%, 4.5% vs. 6.5%). CONCLUSION: Although our study demonstrated that SCN1A is not frequently involved in GEFS+ and FSs, further systemic research would be necessary.

Mutations of SCN1B in Generalized Epilepsy with Febrile Seizures Plus(GEFS+) / 대한소아신경학회지

PURPOSE: Febrile seizures affect 2-5% of all children younger than 6 years old. A small proportion of children with febrile seizures later develop epilepsy. Generalized epilepsy with febrile seizures plus(GEFS+) is an important childhood genetic epilepsy syndrome with heterogeneous phenotypes, including febrile seizures(FS) and generalized epilepsies of variable severity. It was reported that the gene locus for GEFS+ exists in the chromosome 19q13.1, and has relationship with a 387 C->G mutation in the voltage- gated sodium channel beta1 subunit(SCN1B) gene. This study is to determine whether there are mutations in children with GEFS+ and FS. METHODS: Eighteen GEFS+ and thirteen FS patients were screened for mutations in the sodium channel beta-subunits SCN1B. The primer pairs used to amplify the exons of SCN1B are given in the supplementary data on the Neurology web site. All exons were amplified by PCR and PCR products were subsequently sequenced. Single-stranded conformation polymorphism(SSCP) was carried out using 8% polyacrylamide gel. RESULTS: Twenty four patients(77%) were younger than 10 years old, three(10%) were between 10 and 14 years old, and four(13%) older than 14 years old. The ratio of female to male was 0.55:1.0. In phenotypes of GEFS+, fourteen patients(88%) had generalized tonic-clonic seizures, one patient(6%) myoclonic seizures and one patient(6%) atonic seizures. In EEG findings of GEFS+, eleven(78%) patients had normal findings, five(28%) patients generalized spike waves and two patients(11%) diffuse slowings. In sequencing and SSCP of PCR products, we could observe added C mutations between 224G and 225C of exon 3 in two unrelated patients with GEFS+. CONCLUSION: We proved the existence of a new mutation of SCN1B in two unrelated patients with GEFS+.