RESUMO
PURPOSE: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis. METHODS: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models. RESULTS: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity. CONCLUSIONS: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.
Assuntos
Cromossomos Humanos Par 16/genética , Epilepsia Neonatal Benigna/genética , Família , Ligação Genética , Modelos Genéticos , Mutação/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Cromossômico , Cromossomos Humanos Par 19/genética , Eletroencefalografia/estatística & dados numéricos , Epilepsia Neonatal Benigna/diagnóstico , Feminino , Heterogeneidade Genética , Haplótipos , Humanos , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Linhagem , Penetrância , Tomografia Computadorizada por Raios XRESUMO
The purpose of the study was to evaluate the efficacy and safety of topiramate (TPM) as adjunctive therapy in children, adolescents and young adults with Lennox-Gastaut syndrome (LGS). We performed a prospective open label add-on study in 45 patients (age 4-34 years, mean 15.9 years) with LGS and refractory seizures. TPM was added to one or two other baseline drugs and the efficacy was rated according to seizure type and frequency. TPM was initiated at the daily dose of 0.5-1 mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24 h, up to a maximum daily dose of 12 mg/kg. After a mean period of 15.8 months of treatment (range 3-98 months), at a mean dose of 4.1 mg/kg/24 h (range 1.4-12 mg/kg), 18 patients (40%) had a seizure reduction more than 50%. TPM appeared to be effective mainly in major seizures (drop attacks, tonic and tonic-clonic seizures). Mild to moderate adverse events were present in 24 patients (53.3%), mostly represented by drowsiness, nervousness, hyporexia with or without weight loss and cognitive dulling. In conclusion, TPM adjunctive therapy reduced the number of drop attacks and major motor seizures in 40% of patients with LGS and produced only mild or moderate adverse events.