Studies On The Clinical Feature And Gene Diagnosis Of Benign Familial Neonatal Convulsions

Background and objective Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant inherited epileptic syndrome, characterized by unprovoked convulsions. The convulsions typically start around the neonatal period and disappear spontaneously after several weeks or months. Their findings on neuoradiological and plasma biochemical examinations are normal. In the majority of affected individuals longterm development are reported to be normal. BFNC was found to be linked with the mutations of potassium channel subunit gene KCNQ2 and KCNQ3 and pericentric inversion of chromosome 5. Because of the spontaneous regress and excellent prognosis of BFNC, if we diagnose the patient in time, could not only evite the unnecessary examination and treatment and the therapeutic side-effect, but also alleviate tensions of the patient and his family. The gene diagnosis of BFNC not only make us understand the mechanism of BFNC and other epilepsies in the level of molecule, but also is beneficial to genetic consultation,pregnant diagnosis and illness prevention. By clinical data analysis, linkage analysis and the mutation analysis of KCNQ2 gene in three Chinese families, we want to understand the clinic and genetic characteristics of Chinese BFNC and explore the feasibility of its gene diagnosis of BFNC.Methods The clinical datas of three Chinese families were collected and analysed. Six patients' chromosomes were examined. Linkageanalysis were performed in the three families using microsatellite markers D20S430, D20S94, D8S284, D8S558, D8S529, 8S256. DNA sequencing and PCR-single strand conformation polymorphism (PCR-SSCP) analysis were used to detect the gene of KCNQ2 in three probands, other individuals in family 3 and 72 independent control individuals.Results Three families had 20 patients in all and shared the same autosomal dominant inherited pattern. The patients experienced partial or generalized clonic, tonic-clonic or myoclonic convulisons in the age of 2 days to 10 days. Their convulsions disappeared in 18 days to 18 months. Whether were treated or not, their physical and subsequent intellectual development are normal. The interictal electroencephalograph (EEG) of proband in familial 1 presented with bilateral low amplitude, the family 2 proband's interictal EEG was normal.Serum biochemical determinations, image examinations and karyotypes were also normal. Linkage analysis excluded the linkage with KCNQ3 in the three families and hint the linkage with KCNQ2 in family 3, but couldn't exclude the linkage with KCNQ2 in family 1 or in family 2. In the mutation analysis of KCNQ2, we found a mutation of 1931delG in the proband and other patients of family 3, but not in 72 normal controls. In the meantime, we also found three polymorphisms which were 543G?A, 912C?T and 2154T-*A. 543G~"A and 912C-*T have not been reported previously.Conclusions Firstly,the heredity patterns of the three families areall autosomal dormant. Their convulsions started around 2 days to 10 days, disappeared spontaneously in 18 days to 18 months. Their physical examinations and findings on neuoradiologycal and plasma biochemical examinations were normal. There was no other causes of neonatal convulsions. Their longterm development were normal. Therefore, BFNC diagnosis was defined in the three families. Secondly, BFNC can be caused by 1931delG. 1931delG is a new mutation. 543G-*- A and 912C^ T are two new polymorphisms. Thirdly, BFNC has genetic heterogeneity, and may be have another gene locus besides the locuses of KCNQ2 and KCNQ3. Finally, The combination of linkage analysis and gene determination can be used for the gene diagnosis of BFNC.