|Opis:||PURPOSE. Febrile seizures are the most common single seizure disorder in childhood. Both genetic and environmental factors are involved. The candidate genes include genes encoding the composition of the voltage-dependent ionic channel subunits, synaptic receptors in the central nervous system, and genes that affect the mutual recognition of neurons and their interactions. The aim of our study was to contribute some new research information on both clinical and the genetic field. In the latter, we focused on the role of genes SEZ6 and GABRG2, which could be, according to the results of some previous studies, involved in the aetiology of febrile seizures, as well as subsequent epilepsy.
METHODS. 179 children, hospitalized at the Department of Paediatrics Maribor for the first episode of febrile convulsions were included in a prospective study. From the existing medical documentation and some later updating of the medical history, we have obtained information about the clinical parameters. EEG recordings were done in afebrile patients 2 to 3 weeks after the attack. The mean duration of follow-up was 6.6 years (range 2.1 to 9.2 years). The frequency of febrile seizure recurrences and the potential transition to epilepsy were observed. The genomic DNA was isolated from the samples of their blood and the blood samples from 200 healthy adult persons, who represented the control group. The presence of polymorphisms rs209354 in the gene GABRG2 and rs11450637 (cytosine insertion) in the gene SEZ6 were determined by the methods of polymerase chain reaction, agarose gel and capillary electrophoresis. Categorical variables were compared by the chi-square- or Fisher's exact test. Student's t-test was used for normally distributed continuous variables and Mann-Whitney U test for those without normal distribution. The binary regression model was used when appropriate.
RESULTS. Febrile seizure recurred at least once in 58 (32.5%) children. In 32 children (17.9%) there was only one repetition, 26 (14.5%) children had multiple occurrences. Epileptiform EEG discharges were seen in recordings of 30 (16.8%) children. Among them, a half was primary generalized and a half was focal. Epilepsy developed in 12 (6.7%) of children. Among 27 patients in whom the first febrile seizure attack was clinically focal, 5 children (18.5%) had later epilepsy. With the concurrent inclusion of clinical focality and focal epileptiform discharges, epilepsy developed in half of the cases. Low fever at the time of the first febrile seizure episode, the number of repetitions and a positive family history of epilepsy were also associated with a higher risk of the epilepsy occurrence. The risk factors for the recurrence of febrile convulsions were found to be a positive family history of febrile convulsions, low age at the time of the first episode, a repetition of the attack within 24 hours, as well as the focal changes in the EEG. Clinical focality of the attack and low temperature at the time of the first episode were not associated with a higher probability of the first recurrence. However, a significant inverse correlation between the height of the temperature and the number of the recurrences has been demonstrated. The polymorphism in the gene GABRG2 rs209354 and the cytosine insertion in the SEZ6 gene were not associated with a higher probability of recurrence of febrile convulsions, nor with a higher risk of later epilepsy.
CONCLUSIONS. Our most relevant result is statistically significant predictiveness of the EEG focality, in terms of both the likelihood of the recurrence of febrile convulsions and the subsequent transition to epilepsy. In addition, the clinical focality is predictive for later epilepsy. A negative result of the genetic part of the study suggests that the proportion of the influence of individual genes towards the genetic susceptibility to febrile seizures may vary in different populations.|