RESUMO
A novel microdeletion of 14q13.1q13.3 was identified in a patient with developmental delay and intractable epilepsy. The 2.2-Mb deletion included 15 genes, of which TULIP1 (approved gene symbol: RALGAPA1)was the only gene highly expressed in the brain. Western blotting revealed reduced amount of TULIP1 in cell lysates derived from immortalized lymphocytes of the patient, suggesting the association between TULIP1 haploinsufficiency and the patient's phenotype, then 140 patients were screened for TULIP1 mutations and four missense mutations were identified. Although all four missense mutations were common with parents, reduced TULIP1 was observed in the cell lysates with a P297T mutation identified in a conserved region among species. A full-length homolog of human TULIP1 was identified in zebrafish with 72% identity to human. Tulip1 was highly expressed in zebrafish brain, and knockdown of which resulted in brain developmental delay. Therefore, we suggest that TULIP1 is a candidate gene for developmental delay.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 14/genética , Deficiências do Desenvolvimento/genética , Epilepsia Generalizada/genética , Proteínas Ativadoras de GTPase/deficiência , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/deficiência , Sequência de Aminoácidos , Animais , Encéfalo/anormalidades , Encéfalo/embriologia , Criança , Cromossomos Humanos Par 14/ultraestrutura , Códon/genética , Sequência Conservada , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Deficiência Intelectual/genética , Masculino , Dados de Sequência Molecular , Hipotonia Muscular/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Linhagem , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/deficiência , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/fisiologiaRESUMO
PURPOSE: We analyzed sequential changes in the localization of EEG foci along with age to identify a specific EEG pattern, and the relation between the clinical manifestations and the EEG pattern in patients with Panayiotopoulos syndrome (PS). METHODS: The subjects were 76 children, who had been followed up >2 years with repeated EEG examinations at 6-month intervals. Analysis of EEG findings included the determination of localization of spike foci, as a function of age, by using cross-sectional data, and the identification of subgroups with homogeneous EEG patterns. Then we compared certain clinical features among these subgroups. RESULTS: In the cross-sectional EEG study, the occipital EEG spike focus was most frequently seen between ages 2 and 5 years. Independent and synchronous frontopolar and occipital spikes (Fp-O spikes) and centroparietotemporal (CPT) EEG spike foci had increased incidences between ages 4 and 7 years, and between ages 6 and 10 years, respectively. We subclassified the 76 patients into the following five subgroups based on the evolutional changes in epileptic EEG foci, which frequently showed shifting, multiplications, and generalization: (a) persistent occipital focus group (O group), (b) Fp-O spikes group (Fp-O pattern group), (c) generalized EEG pattern group, (d) CPT foci group (CPT group), and (e) no epileptic EEG focus group. The Fp-O group showed the latest age at onset of epilepsy. The generalized EEG pattern group had the highest frequency of seizures as well as recurrences of status epilepticus (SE), as well as the longest active seizure period among the five groups. CONCLUSIONS: These results indicated that the EEG foci in most of patients with PS are frequently shifting location, multiplying, and propagating diffusely with age, rather than persistently localizing in the occipital region. In addition, the EEG patterns showed a certain trend and roughly corresponded to certain clinical characteristics. However, the prognosis of the seizures appeared to be favorable regardless of the EEG pattern.
Assuntos
Córtex Cerebral/fisiopatologia , Eletroencefalografia/estatística & dados numéricos , Epilepsias Parciais/diagnóstico , Fatores Etários , Idade de Início , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Biomarcadores , Mapeamento Encefálico , Criança , Pré-Escolar , Estudos Transversais , Eletroencefalografia/métodos , Epilepsias Parciais/fisiopatologia , Epilepsia Rolândica/diagnóstico , Epilepsia Rolândica/fisiopatologia , Feminino , Seguimentos , Lateralidade Funcional , Humanos , Lactente , Masculino , Lobo Occipital/fisiopatologia , Prognóstico , SíndromeRESUMO
We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age of 10, followed by truncal hypertonia and progressive scoliosis after 1 year. He had bizarre involuntary movement of his limbs upon waking, which was initially misinterpreted as a psychogenic reaction. Routine neurological examinations revealed no abnormality. Treatment with diazepam, bacrophen, 1-dopa, and clonazepam, led to only short time improvement of symptoms. At the age of 14, his symptoms gradually improved in natural course. At present he is 15 years old, and capable of normal daily activities. His clinical course was not typical of idiopathic torsion dystonia and very rare in children.
Assuntos
Blefarospasmo/etiologia , Distonia Muscular Deformante/complicações , Blefarospasmo/fisiopatologia , Criança , Distonia Muscular Deformante/fisiopatologia , Eletromiografia , Humanos , MasculinoRESUMO
This study investigated the clinical and EEG characteristics of initial status epilepticus (SE) during infancy in patients with mesial temporal lobe epilepsy (MTLE). The subjects were six patients who had been brought to our emergency clinic and treated for their initial SE between 1977 and 1988, and later developed MTLE. We reviewed the medical records and laboratory findings at the time of the initial SE, and the clinical evolution up to the development of MTLE. The six patients included four females and two males. The initial SE developed at ages ranging from 7 months to 2 years and 9 months with a mean of 1 year and 2 months. These episodes were characterized by an elevated temperature of more than 38 degrees C (4/6 cases), clusters of prolonged seizures during one episode of SE (4/6 cases), long-lasting SE (120-380 min, mean 227 min, 6/6 cases), postictal prolonged loss of consciousness (median 5 h, 6/6 cases), and the presence of Todd's paralysis (3/6 cases). The lateralization of the ictal or postictal EEGs of the SE in five of the six cases was identical to that of the hippocampal atrophy later confirmed by MRI. Follow-up EEG examinations at a 6 month interval demonstrated temporal spike discharges appearing only after the onset of complex partial seizures. Two patients, who had no fever at the initial SE, were characterized by a very early appearance of epileptic EEG abnormality and a short interval between the initial SE and the development of complex partial seizures, suggesting that the SE was the first epileptic manifestation. The result of this study showed that SE progressing to MTLE tends to have complicated clinical manifestations characterized by clusters of unilateral or generalized SE followed by prolonged postictal unconsciousness, generalized clinical manifestations despite lateralized ictal EEG discharges, and the Todd's paresis in addition to the prolonged seizure duration.