RESUMO
Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures.
Assuntos
Proteínas Serina-Treonina Quinases/genética , Síndrome de Rett/genética , Transtornos dos Cromossomos Sexuais , Idade de Início , Deficiências do Desenvolvimento , Seguimentos , Humanos , Lactente , Masculino , Mutação , Convulsões/genética , Inativação do Cromossomo XRESUMO
Glucose transporter type 1 deficiency syndrome (Glut1 DS) is a rare neurological disorder caused by impaired glucose delivery to the brain. The clinical spectrum of Glut1 DS mainly includes epilepsy, paroxysmal dyskinesia (PD), developmental delay and microcephaly. Glut1 DS diagnosis is based on the identification of hypoglycorrhachia and pathogenic mutations of the SLC2A1 gene. Here, we report the molecular screening of SLC2A1 in 354 patients clinically suspected for Glut1 DS. From this cohort, we selected 245 patients for whom comprehensive clinical and laboratory data were available. Among them, we identified 19 patients carrying nucleotide variants of pathological significance, 5 of which were novel. The symptoms of onset, which varied from neonatal to adult age, included epilepsy, PD or non-epileptic paroxysmal manifestations. The comparison of the clinical features between the 19 SLC2A1 mutated and the 226 non-mutated patients revealed that the onset of epilepsy within the first year of life (when associated with developmental delay or other neurological manifestations), the association of epilepsy with PD and acquired microcephaly are more common in mutated subjects. Taken together, these data confirm the variability of expression of the phenotypes associated with mutation of SLC2A1 and provide useful clinical tools for the early identification of subjects highly suspected for the disease.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos , Coreia , Deficiências do Desenvolvimento , Epilepsia , Transportador de Glucose Tipo 1/genética , Deficiência Intelectual , Microcefalia , Proteínas de Transporte de Monossacarídeos/deficiência , Adolescente , Adulto , Erros Inatos do Metabolismo dos Carboidratos/complicações , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/genética , Criança , Pré-Escolar , Coreia/etiologia , Coreia/genética , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/genética , Epilepsia/etiologia , Epilepsia/genética , Feminino , Humanos , Lactente , Deficiência Intelectual/etiologia , Deficiência Intelectual/genética , Masculino , Microcefalia/etiologia , Microcefalia/genética , Proteínas de Transporte de Monossacarídeos/genética , Fenótipo , Adulto JovemRESUMO
We report the case of a five-year-old girl, presenting with difficult-to-treat, symptomatic focal epilepsy, who developed status gelasticus following the introduction of levetiracetam as add-on treatment to oxcarbazepine and diazepam. Gelastic seizures were documented by video-EEG and were responsive to i.v. administration of diazepam. A possible causative role of levetiracetam is suggested. Specific susceptibility to some AEDs is also discussed, as this patient, at the age of four years, had presented an episode of non-convulsive status epilepticus, following introduction of tiagabine, in association with vigabatrin and nitrazepam.[Published with video sequences].