Abstracts

Rationale: Status epilepticus (SE) may present as an isolated episode in normal infants during a febrile illness. On the other side, it may be repeatedly observed in severe epileptic syndromes of infancy, such as Dravet syndrome, with which the differential diagnosis is difficult initially. Abnormalities on the gene that encodes SCN1a, are found in 70-80% of patients with classic Dravet syndrome. The objective of this study was to analyze the frequency and nature of SCN1a abnormalities and to identify potential predictive factors for the development of Dravet syndrome in a population of children who presented at least one episode of SE. Methods: Children who presented with at least one episode of SE between 1 month and 16 years, were included. These children were selected in a larger group of children with seizures in which SCN1a was analyzed. To detect any partial or complete deletion/duplication on SCN1a, multiplex ligation-dependent probe amplification was performed. Prescreening for potential DNA point mutations was carried out by high-resolution melting curve analysis (HRMCA). SCN1a was divided in 40 fragments. DNA from patients was tested in parallel with DNA from control patients. Normalized and temperature-shifted difference plots were compared between samples. Fragments showing abnormal HRMCA profiles were amplified by pcr. Direct sequencing of the purified products was performed and further analyzed on capillary electrophoresis using primers designed to cover all exons and their flanking sequences. Blood samples from the parents of children with abnormal genetic results were analyzed. Results: 110 children were tested for SCN1a mutations. 73 of them who presented with at least one episode of status epilepticus were included in this study. SCN1a abnormalities were found in a total of 14 patients and in 11 (15%) of those with SE. Nine (82%) of the latter had Dravet syndrome, and 2 (18%) were on the GEFS+ spectrum. All of those with abnormal SCN1a results who later developed Dravet syndrome were boys; their mean age at initial SE was 9 months. Abnormalities were de novo in 6 Dravet patients, unknown in 2 (parents not tested, and inherited in one (mutation unlikely to be causal per se). The initial SE was hemiclonic in four, and five had apparently generalized tonic-clonic convulsions. One girl with Dravet phenotype but negative SCN1a analyses presented with SE at 36 months. Conclusions: In our study, the risk of developing Dravet syndrome after an initial SE episode was particularly high in boys whose initial SE episode was observed between 6-18 months. One girl with Dravet phenotype and negative SCN1a analysis presented with SE at 36 months. These results indicate that performing SCN1a analysis may be warranted in every child who presents with an initial episode of SE at less than 18 months. This may help in the early diagnosis and management of Dravet syndrome. Our results also carry fundamental prognostic value, and may optimize genetic counseling. In addition, SCN1a testing is unlikely to be useful if the initial SE episode is observed after 36 months.