RESUMEN
Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.
As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.
Asunto(s)
Neurología , Niño , Adolescente , Humanos , BrasilRESUMEN
Abstract Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.
Resumo As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.
RESUMEN
OBJECTIVE: To present a cohort of 8 males and perform a systematic review of all published cases with a single copy of MECP2 carrying a pathogenic variant. METHODS: We reviewed medical records of males with a single copy of MECP2 carrying a pathogenic variant. We searched in Medline (Pubmed) and Embase to collect all articles which included well-characterized males with a single copy of MECP2 carrying a pathogenic or likely pathogenic variant in MECP2 (1999-2020). RESULTS: The literature search yielded a total of 3,185 publications, of which 58 were included in our systematic review. We were able to collect information on 27 published patients with severe neonatal encephalopathy, 47 individuals with isolated or familial mental retardation X-linked 13 (XLMR13), as well as 24 individuals with isolated or familial Pyramidal signs, parkinsonism, and macroorchidism (PPM-X). In our cohort, we met eight individuals aged 4 to 19-year-old at the last evaluation. Three MECP2-associated phenotypes were seen in male carriers of a single copy of the gene: severe neonatal encephalopathy (n = 5); X-linked intellectual deficiency 13 (n = 2); and pyramidal signs, parkinsonism, and macroorchidism (PPM-X) (n = 1). Two novel de novo variants [p.(Gly252Argfs∗7) and p.(Tyr132Cys)] were detected. CONCLUSION: In males, the MECP2 pathogenic variants can be associated with different phenotypes, including neonatal severe encephalopathy, intellectual deficiency, or late-onset parkinsonism and spasticity. The typical RS phenotype is not expected in males, except in those with Klinefelter syndrome or somatic mosaicism for MECP2.
Asunto(s)
Encefalopatías , Discapacidad Intelectual , Síndrome de Rett , Adolescente , Adulto , Niño , Preescolar , Genes Ligados a X , Humanos , Discapacidad Intelectual/genética , Masculino , Proteína 2 de Unión a Metil-CpG/genética , Mutación , Fenotipo , Síndrome de Rett/genética , Adulto JovenAsunto(s)
Encefalopatías/genética , Mosaicismo , Canal de Sodio Activado por Voltaje NAV1.3/genética , Trastornos del Neurodesarrollo/genética , Canales de Sodio/genética , Encefalopatías/diagnóstico , Niño , Preescolar , Mutación de Línea Germinal , Humanos , Lactante , Masculino , Trastornos del Neurodesarrollo/diagnóstico , LinajeRESUMEN
INTRODUCTION: KCNT2 was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. CASE REPORT: We present an additional observation of a 16-year-old male patient with a novel de novo KCNT2 likely pathogenic variant and review the five previously reported cases of de novo variants in this gene. DISCUSSION: Whole exome sequencing identified the missense variant c.725Câ¯>â¯A p.(Thr242Asn), which was confirmed by Sanger sequencing. Our patient has a refractory stereotyped and monomorphic type of hyperkinetic focal motor seizure, similar to what is seen in frontal lobe epilepsy, occurring only during sleep. This type of seizure is not usually seen in epileptic encephalopathies.
Asunto(s)
Encefalopatías/genética , Epilepsia del Lóbulo Frontal/genética , Canales de potasio activados por Sodio/genética , Adolescente , Encefalopatías/metabolismo , Niño , Epilepsia del Lóbulo Frontal/diagnóstico , Epilepsia Generalizada/genética , Femenino , Humanos , Masculino , Mutación Missense/genética , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/genética , Fenotipo , Canales de potasio activados por Sodio/metabolismo , Secuenciación del Exoma , Adulto JovenRESUMEN
ATP6V1B2 encodes a subunit of the lysosomal transmembrane proton pump necessary for adequate functioning of several acid hydrolases. De novo monoallelic variants of this gene have been associated with two distinct phenotypes: Zimmermann-Laband syndrome 2 (ZLS2), an intellectual deficiency/multiple malformation syndrome, and dominant deafness onychodystrophy (DDOD), a multiple malformation syndrome without cognitive involvement. Epilepsy is not observed in DDOD, is variably present in ZLS2, but is a common feature in Zimmermann-Laband syndrome 1 (ZLS1) (caused by monoallelic pathogenic variants in KCNH1) and Zimmermann-Laband syndrome-like (ZLSL) (associated with KCNK4 variants). Herein, we report a case of an infant with severe epileptic encephalopathy with microcephaly and profound developmental delay, associated with a novel de novo loss-of-function variant in ATP6V1B2, diagnosed by whole-exome sequencing. This finding expands the spectrum of ATP6V1B2-associated disorders and adds ATP6V1B2 as a new member for the growing list of early-onset epileptic encephalopathy genes. [Published with video sequence].
Asunto(s)
Discapacidades del Desarrollo/genética , Epilepsia/genética , Microcefalia/genética , ATPasas de Translocación de Protón Vacuolares/genética , Humanos , Recién Nacido , Síndrome , Secuenciación del ExomaRESUMEN
SCN3A was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. We present two additional patients with a novel de novo SCN3A pathogenic variant, and a review of all published cases of de novo variants. In one of our patients brain magnetic resonance imaging (MRI) disclosed a severe polymicrogyria and in the other it was normal. The clinical phenotype was characterized by a severe developmental delay and refractory epilepsy in the patient with polymicrogyria and intellectual disability with autistic features and pharmacoresponsive epilepsy in the subject with normal MRI. Polymicrogyria, a disorder of progenitor cells proliferation and migration, is an unanticipated finding for an ion channel dysfunction.
Asunto(s)
Canal de Sodio Activado por Voltaje NAV1.3/genética , Trastornos del Neurodesarrollo/genética , Canales de Sodio/genética , Preescolar , Epilepsia/genética , Femenino , Genotipo , Humanos , Discapacidad Intelectual/genética , Imagen por Resonancia Magnética , Masculino , Mutación/genética , Canal de Sodio Activado por Voltaje NAV1.3/metabolismo , Trastornos del Neurodesarrollo/fisiopatología , Fenotipo , Polimicrogiria/genética , Canales de Sodio/metabolismoRESUMEN
BACKGROUND: Hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and multiple seizure types. Hemispheric surgery is indicated for patients with unilateral intractable epilepsy. Although described more than 50 years ago, several new techniques for hemispherectomy have only recently been proposed aiming to reduce operatory risks and morbidity. MATERIALS AND METHODS: We present the clinical characteristics, presurgical workup, and postoperative outcome of a series of pediatric patients who underwent hemispherectomy for medically intractable epileptic seizures. Thirty-nine patients with medically intractable epilepsy underwent surgery from 1996 to 2005. RESULTS AND DISCUSSION: We analyzed demographic data, interictal and ictal EEG findings, age at surgery, surgical technique and complications, and postsurgical seizure outcome. There were 74.4% males. Tonic and focal motor seizures occurred in 30.8 and 20.5% of the patients. Most frequent etiologies were Rasmussen encephalitis (30.8%) and malformation of cortical development (23.1%). Postsurgical outcomes were Engel classes I and II for 61.5% of the patients. In general, 89.5% of the patients exhibited at least a 90% reduction in seizure frequency. All patients had acute worsening of hemiparesis after surgery. Basically, two surgical techniques have been employed, both with similar results, although a trend has been noted toward one of the procedures which produced consistently complete disconnection. Patients with hemispheric brain lesions usually have abnormal neurological development and intractable epilepsy. When video-EEG monitoring and magnetic resonance imaging show unilateral disease, the patient may evolve with a good surgical outcome. We showed that a marked reduction in seizure frequency may be achieved, with acceptable neurological impairments.