Genetic analysis and prenatal diagnosis of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 due to variants of PIGT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents.@*METHODS@#A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci.@*RESULTS@#The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor.@*CONCLUSION@#The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.

Early identification and diagnosis of epilepsy related to fever sensitivity / 中国当代儿科杂志

Febrile seizures are the most common nervous system disease in childhood, and most children have a good prognosis. However, some epilepsy cases are easily induced by fever and are characterized by "fever sensitivity", and it is difficult to differentiate such cases from febrile seizures. Epilepsy related to fever sensitivity includes hereditary epilepsy with febrile seizures plus, Dravet syndrome, and

Síndromes epilépticos genéticos / Genetic epileptic syndromes

Resumen Pediátr Panamá 2017; 46 (2): 68-74 Resumen La epilepsia es uno de los trastornos neurológicos crónicos más frecuentes, afectando 1-1.5% de la población mundial. Más de la mitad de los casos están relacionados a una causa genética. Avances en el área de genética y epilepsia, han revolucionado nuestro conocimiento acerca de la relación genotipo-fenotipo de los diferentes síndromes epilépticos. La mayoría de genes descubiertos causan epilepsias monogenéticas raras que obedecen a un patrón de herencia Mendeliano. La era del descubrimiento genético en el área de epilepsia, inicia con el hallazgo de genes implicados en el funcionamiento de los canales iónicos: "Epilepsia Autosómica Dominante Nocturna del Lóbulo Frontal" asociada al gen CHRNA4 y la "Epilepsia Generalizada con Convulsiones Febriles Plus (GEFS+) asociada a los genes SCN1A, SCN1B. Posteriormente se descubren genes que no solo afectan canales iónicos, pero que inter eren con otros procesos celulares: tráfico de membrana (STXBP1, STX1 B), transporte (SLC2A1, SLC1A2), moléculas de adhesión celular (PCDH19, CNTN2), modulares enzimáticos (TBC1D24, DOCK7), etc. Desde el punto de vista clínico, un diagnóstico específico, podría modificar el tratamiento: introducción de dieta cetogénica en el caso de GLUT 1, evitar el uso de bloqueadores de canales de sodio en Dravet o evitar valproato en pacientes con mutaciones en POLG 1. Este artículo revisará los diferentes síndromes genéticos asociados con epilepsia y los avances realizados en el área de genética -epilepsia.

Abstract Epilepsy is one of the most common chronic neurologic disorders, affecting 1-1.5% of the population. More than half of the cases have a genetic etiology. Advances in the field of genetics and epilepsy, improved our understanding about the genotype - phenotype relationship of the different epileptic syndromes. The majority of genes discovered cause rare monogenetic epilepsies with Mendelian inheritance. The era of genetic discovery started with the finding of genes associated with channel function: "Autosomal Dominant Nocturnal Frontal Lobe Seizures" linked to the CHRNA4 gene and "Genetic Epilepsy, Febrile Seizures plus (GEFS+)" associated with SCN1A and SCN1B genes. Subsequently, new genes affecting different cellular processes other than ion channels were discovered. These include: Membrane tracking (STXBP1, STX1 B), transport (SLC2A1, SLC1A2), Cellular adhesion molecules (PCDH19, CNTN2), enzyme modulators (TBC1D24, DOCK7), etc. From the clinical standpoint, obtaining the specific genetic diagnosis could modify treatment: implementation of ketogenic diet in the case of GLUT1, avoiding sodium channel blocker medications in Dravet Syndrome or avoiding Valproate in patients with POLG 1 mutations. This article will review the different genetic epilepsy syndromes and the new discoveries in the field of genetics and epilepsy.

Late-onset childhood occipital epilepsy. An unusual case in adolescence and differential diagnosis with migraine / Epilepsia occipital da infância de início tardio

INTRODUCTION: The new proposed classification of ILAE Task Force (2001) proposes that the occipital epilepsies should be split into two subtypes: an early-onset benign childhood occipital epilepsy (or Panayiotopoulos type) and late-onset childhood occipital epilepsy (or Gastaut type). Migraine with visual aura must be considered as a differential diagnosis in childhood and adolescents with occipital epilepsy without motor phenomena. OBJECTIVE: The goal of our paper is to report the case a 16-year-old female, with normal psychomotor development, that during the lunch time presented an event characterized by the vision of multiple colored spots which were moving horizontally and vertically and also in circles through the visual field. Minutes after the visual event, the patient referred to a severe diffuse throbbing headache with frontal predominance. During the clinical investigation was submitted to a video-electroencephalogram exam for 12 hours with, reveling occipital sharp-waves discharges in occipital right region as well as in occipital left region. CONCLUSION: We reported of such classic type of epileptic syndrome in a patient in the unusual age of onset, the end of adolescence, considering the differential diagnosis with migraine with visual aura.

INTRODUÇÃO: A nova proposta de classificação da ILAE (2001) propõe que as epilepsias occipitais sejam classificadas em dois subtipos: epilepsia occipital benigna da infância de início precoce (ou tipo Panayiotopoulos) e epilepsia occipital benigna da infância de início tardio (ou tipo Gastaut). A migrânia com aura visual deve ser considerada como um diagnóstico diferencial nas crianças e nos adolescentes com epilepsia occiptal sem fenômenos motores associados. OBJETIVO: relatar o caso de uma paciente do sexo feminino de 16 anos, com desenvolvimento neuropsicomotor normal, que durante o almoço apresentou um evento caracterizado pela visão de múltiplas manchas coloridas que se movimentavam no sentido horizontal e vertical e também em círculos no seu campo visual. Minutos após este evento visual, a paciente passou a referir cefaléia difusa com predomínio frontal. Durante a investigação clínica foi submetida à realização de vídeo-eletrencefalograma com 12 horas de duração revelando descargas de ondas agudas ora na região occipital direita ora na região occipital esquerda. CONCLUSÃO: apresentamos um tipo clássico de síndrome epiléptica iniciando em uma idade pouco usual, o final da adolescência, considerando o diagnóstico diferencial com a migrânia com aura visual.

Tratamento das epilepsias generalizadas idiopáticas / Idiopathic generalized epilepsies treatment

As epilepsias generalizadas idiopáticas (EGIs) correspondem a um-terço de todas as epilepsias. Apesar desta elevada freqüência, as EGIs permanecem pouco reconhecidas. As características clínicas são fundamentais para o diagnóstico. Neste grupo de epilepsias, todos os tipos de crises generalizadas podem ocorrer especialmente as crises tônico-clônicas generalizadas, as crises mioclônicas e as crises de ausência. O eletroencefograma é bastante sugestivo do diagnóstico quando evidencia os típicos complexos espículas ou poliespículas-onda lenta, generalizados, simétricos e com atividade de base normal. De acordo com o tipo de crise predominante e com a idade de início das crises, as EGIs são divididas em subsíndromes. A importância do diagnóstico preciso está relacionada com a elevada porcentagem de indivíduos livre de crises quando tratados com a medicação antiepiléptica apropriada. Por outro lado, o uso de algumas medicações antiepilépticas como carbamazepina e fenitoína pode exacerbar as crises ou até mesmo induzir estado de mal epiléptico em determinadas subsíndromes. Neste artigo, revisamos as principais medicações antiepilépticas utilizadas no tratamento das EGIs bem como alguns aspectos práticos no tratamento das subsíndromes mais freqüentes.

Idiopathic generalized epilepsies (IGEs) correspond to one-third of all epilepsies. Despite of this high frequency, IGEs remains underdiagnosed. Clinical features are the cornerstone to diagnosis. In this group all types of generalized seizures may occur such as generalized tonic-clonic, absences and myoclonic seizures. EEG is very supportive of IGEs diagnosis when it shows the typical generalized symmetrical, spike or polispyke and waves complexes with normal background. According to the main seizure type and the age of onset, IGEs are divided in subsyndromes. The importance of the correct diagnosis is supported by the high rate of seizure free patients under appropriate antiepileptic drug therapy. On the other hand, the use of some antiepileptic drugs such as carbamazepine or phenytoin may exacerbate the seizures or even induce status epilepticus in some subsyndromes. In this article, the main antiepileptic drugs used in the treatment of IGEs are reviewed as well as some practical issues for IGEs subsyndromes treatment.

Transtornos psiquiátricos na epilepsia: uma proposta de classificação elaborada pela comissão de neuropsiquiatria da ILAE: [revisão] / Psychiatric disorders in epilepsy: a proposal for classification by the ILAE commission on neuropsychiatry: [review]

INTRODUÇÃO: Um dos aspectos mais importantes da epileptologia é o da sua relação com as comorbidades psiquiátricas. Transtornos psiquiátricos (TP) são associados a praticamente todas as síndromes epilépticas e contribuem para uma maior dificuldade no manejo desses pacientes. OBJETIVO: O presente trabalho tem como objetivo fazer uma revisão das classificações dos TP na epilepsia e destacar a proposta elaborada pela Comissão de Neuropsiquiatria da ILAE. CONCLUSÃO: A proposta de classificação elaborada pela ILAE procurou diferenciar os TP que ocorrem em comorbidade daqueles que refletem atividade epileptiforme ou que ocorrem especificamente na epilepsia, sendo baseada em aspectos clínicos e descritivos mais do que em etiologias. Apresenta ainda critérios bastante claros e operacionais, constituindo-se de grande utilidade para futuros estudos dos quadros psiquiátricos na epilepsia.

INTRODUCTION: The relationship between psychiatric disorders (PD) and epilepsy is among the most frequent and important aspects of epileptology. PD are present in all epileptic syndromes and contribute to increase the difficulties in treating these patients. OBJECTIVE: We reviewed the classifications for the PD in epilepsy and highlighted the proposal by the ILAE Commission on Neuropsychiatry. CONCLUSION: The classification proposal by the ILAE attempted to separate disorders comorbid with epilepsy and those that reflect ongoing epileptiform activity from epilepsy-specific disorders and are based on clinical and descriptive symptoms rather than in etiological classification. It also presents clear and operational criteria that could be of greater utility for future studies of PD in epilepsy.

Pesquisa em epilepsia na infância / Research in epilepsy in the childhood

Este relato pretende divulgar a pesquisa em epilepsia na infância realizada por diferentes centros no nosso país. Estas informações foram apresentadas durante o Fórum Nacional de Epilepsia (XX Congresso Brasileiro de Neurofisiologia Clínica), e ilustram os esforços de cada grupo para promover pesquisa e conhecimentos sobre epilepsia em populações pediátricas. Os principais temas pesquisados incluem epidemiologia, eletrencefalografia, genética e aspectos cognitivos em crianças com epilepsia, estudos controlados de drogas antiepilépticas em diferentes síndromes epilépticas da infância, dieta cetogênica, crises únicas e crises febris, epilepsia do lobo frontal e do lobo temporal, síndrome de West e espasmos infantis, estado de mal epiléptico, malformações do desenvolvimento cortical, sono e epilepsia, cirurgia de epilepsia, co-morbidade psiquiátrica e aspectos de neuroimagem associados à epilepsia na infância. Alguns centros relataram a realização de estudos colaborativos envolvendo diferentes instituições, uma importante ferramenta para o desenvolvimento da pesquisa em epilepsia na infância em nosso país.(AU)

This report describes current pediatric epilepsy research carried out in Brazilian academic centers, presented at the National Epilepsy Forum, during the XX Brazilian Clinical Neurophysiology Congress. It illustrates the different groups’ efforts to promote research and increase awareness of epilepsy in the pediatric population. Main current research lines include epidemiology, electroencephalography, genetic and cognitive issues in pediatric epilepsy, controlled clinical trials with antiepileptic drugs in different childhood epileptic syndromes, ketogenic diet, single and febrile seizures, temporal and frontal lobe epilepsy, West syndrome-infantile spasms, status epilepticus, malformations of cortical development, sleep and epilepsy, epilepsy surgery in childhood, psychiatric co-morbities and neuroimaging in childhood epilepsy. Collaborative studies, an important tool in fostering research in pediatric epilepsy in our country, are being carried out by some academic centers.(AU)