Background Severe myoclonic epilepsy in infancy (SMEI) is a severe form of generalized epilepsy with febrile seizures (GEFS+). SMEI is a rare disorder characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development stagnates around the second year of life. SME is considered to be the most severe phenotype within the spectrum of GEFS+. SME is a malignant epileptic syndrome, while GEFS+ is usually benign. An autosomal dominant pattern of inheritance is observed with GEFS+. SCN1A-related seizure disorders encompass a spectrum that ranges from simple febrile seizures (FS) and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end Patients and methods 87 infants representing GEFS+ were analyzed by bidirectional sequencing of all exons of the SCN1A, SCN2A, GABRG2 or SCN1B genes. Additionally, MLPA analysis of SCN1A was performed. Results In 36 patients with disease causing mutations were characterized. 34 mutations were found in SCN1A and two in GABRG2. 9 mutations were found in relatives. Discussion The majority of the patients presenting with missense mutations had a less severe form of GEFS+. In all but one case the mutation positive relatives belong to this group. The majority of the relatives had no phenotypic manifestations. The patients with nonsense, splice site or frameshift mutations or large deletions had phenotypes in the SMEI end of the clinical spectra. All but 2 of the missense mutations were new. Mutations giving rise to the SMEI phenotype represent de novo incidences.
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11th International Symposium on Mutations in the Genome 6 - 10 June 2011 Santorini, Greece