Abstracts

Rationale: Mutations in the SCN1A gene have been identified in a variety of epilepsy phenotypes, from severe encephalopathies such as Dravet syndrome (DS) to milder familial forms such as generalized epilepsy with febrile seizures plus. In a previous study, a SCN1A mutation was also identified in a patient with Lennox-Gastaut syndrome (LGS), and the aim of our study was to investigate the importance of mutations in the SCN1A gene in Norwegian patients with clinical features of LGS. Methods: We screened 22 adult patients for SCN1A mutations by direct sequencing of DNA extracted from peripheral blood and for micro rearrangements with multiplex ligation-dependent probe amplification (MLPA). If a mutation or rearrangement was identified, the parents of the patient and 106 healthy, unrelated Norwegian control individuals were tested for the same mutation or rearrangement. Results: Sequencing of the SCN1A gene revealed one de novo heterozygous point mutation in one of the patients. The mutation is located in intron 2, c.383+1A>G, affecting a donor splice site. The mutation was not detected in the parents of the patient, nor in any of the 106 healthy, unrelated Norwegian control individuals tested. MLPA did not reveal any copy number changes in the gene in any of the 22 patients. Conclusions: Although SCN1A mutations might not be a common cause of LGS, our finding emphasizes the importance of SCN1A mutations also in childhood encephalopathies without the classical clinical picture of DS, in particular in cases with overlapping elements of LGS. Possibly, a number of individuals with an LGS diagnosis considered to have the myoclonic variant of the disorder may harbour SCN1A mutations, particularly patients who were born before DS was recognized or in a time when the awareness of this syndrome was limited. The confirmation of an SCN1A mutation might have important implications for seizure management and genetic counseling at any age.