Study Of The Spectrum Of Febrile Seizures Related Epilepsy And Its Possible Genetics

Purpose To study the clinical features of febrile seizures related epilepsy, screen SCN1A, SCN2A, SCN1B, GABRG2 genes mutation in 160 Chinese probands and explore the possible relationship between the phenotype and genotype.Methods Study was done in 2659 patients with epilepsy visiting our epileptic clinic during 2004-2007. According to criteria of the International League against Epilepsy (ILAE), FS, SMEI, MAE were diagnosed; according to international criteria, GEFS+, SMEB, ICEGTC were diagnosed; and the diagnosis of PEFS+ was made based on the partial seizures. The information of clinical manifestation, EEG, brain imaging, psychiatric development, treatment and prognosis were collected and analyzed. DNA of the febrile related epilepsy patients were extracted from peripheral blood. All exons of SCN1A, SCN2A, SCN1B and GABRG2 genes were screened with denaturing high performance liquid chromatography (DHPLC) technology, and then sequence analysis was performed on those with abnormal elution peak.Results 160 patients were collected, among these there were 24 (male 20, female 4) SME (12 SMEI and 12 SMEB), 34(male 31, female 13) GEFS+, 85(male 50, female 35) PEFS+, 15(male 6, female 9) FS and 2(male 1, female 1) MAE, the sex ration between male and female was 1.58:1. 71 patients had family history of febrile seizures or epilepsy, which was 44.4%, 7 in SME, 29.2%; 15 in GEFS+, 44.1%; 39 in PEFS+, 45.9%; 9 in FS, 60%; 1 in MAE, 50%. All patients had multiple seizure types, generalized seizures included tonic-clonic, myoclonic, absence, tonic and atonic seizures. Parital seizures included CPS, sGTCS, SPS and unilateral clonic seizures. Some of the patients had different degrees of mental developing retardation, some had abnormality on brain imaging. On medicine treatment, VPA, TPM and CNZ were the most effective medicines. LTG and CBZ could be beneficial or aggravated. The screening of SCN1A, SCN2A, SCN1B, GABRG2 genes among these 60 patients found out that 20 mutations in SCN1A, 1 mutation in SCN2A. 8 mutations were found in SME patients, percentage of mutation was 33.3%, 10 mutations in PEFS+ patients, percentage was 11.7%, 2 mutation in FS patients, percentage was 6.7%, 1 mutation in GEFS+, percentage was 2.9%. No mutation was found in MAE patients. There was no abnormality on SCN1B and GABRG2 screening。In 2 PEFS+ probands with SCN1A mutation, mosaic mutation was found in the fathers.Conclusions Febrile related epilepsy is a disease covers wide range of many epileptic syndromes, from the benign FS to malignant SME, and the clinical phenotype is multiple, includes almost all the epileptic seizures types. From the screening result of 4 genes, SCN1A is the most closed related gene with febrile related epilepsy, and the highest mutation percentage was in SME patients, suggested that SCN1A should be the main pathogenic gene to SME.