A Importância de Brincar

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IDIOPATHIC TOE WALKING IN CHILDREN AND ADOLESCENTS

A marcha em pontas tem uma incidência de 7-24% na popu¬lação pediátrica em geral e é uma causa relativamente frequente de referenciação à consulta de neurologia pediátrica. A marcha em pontas idiopática ocorre em crianças saudáveis, sem espas¬ticidade e com reflexos osteotendinosos normais; é evidente desde o início da marcha autónoma, sempre bilateral e não pro¬gressiva. A sua etiologia é desconhecida, pelo que se trata de um diagnóstico de exclusão. Assim, na avaliação destas crian¬ças é essencial estar alerta para sinais sensoriais ou motores, pois este padrão de marcha pode ser o primeiro sinal de patolo¬gia tal como paralisia cerebral, distrofia muscular congénita ou perturbação do espectro do autismo. As opções terapêuticas passam por tratamentos conservadores, como fisioterapia, uti¬lização de calçado formativo, talas ou ortóteses, ou tratamen¬tos mais invasivos, como uso de gessos seriados, aplicação de toxina botulínica ou cirurgia. Neste artigo de atualização pretende-se: abordar alguns aspetos epidemiológicos e fisiopatológicos, rever a apresenta¬ção clinica e diagnósticos diferenciais e propor orientações para o seguimento e tratamento em idade pediátrica.Toe walking has an estimated incidence of 7-24% in the general pediatric population and is a frequent cause of referral to outpatient pediatric neurology. Idiopathic toe walking occurs in healthy children without spasticity and normal osteotendinous reflexes, is evident from the beginning of independent gait and always bilateral and not progressive. The etiology is unknown, so it is a diagnosis of exclusion. Thus, in evaluating these children is essential to be alert to sensory or motor signs because this gait pattern may be the first sign of pathologies such as cerebral palsy, congenital muscular dystrophy or autism spectrum disorder. Therapeutic options include more conservative treatments such as physiotherapy, use of orthopedic footwear, splints or orthotics; or more invasive treatments such as use of serial casts, botulinum toxin or surgery. The aim of this article is: to address epidemiological and pathophysiological aspects, review the clinical presentation and differential diagnosis and propose guidelines for the monitoring and treatment of idiopathic toe walking in pediatric age

Síndrome de Dravet − experiência de uma Unidade de Neuropediatria

Introduction: Dravet syndrome (DS) is a rare and complex genetic epilepsy syndrome. The first seizures are generally induced by fever in the first year of life of a previously healthy child, and the condition is typically associated with impaired psychomotor development. The authors present a clinical review of DS patients followed at a Neuropediatric Unit of a level III Pediatric Hospital. Material and methods: Retrospective study of pediatric patients with DS followed at a Neuropediatric Unit between 2001 and 2019. Results: Twenty-two patients were diagnosed and followed in this institution. The median (interquartile range [IQR]) age at first seizure was 4.5 (4-5.75) months, which was described as generalized tonic-clonic, focal seizure, or focal to bilateral tonic-clonic seizure, and 95% of patients had fever during this first episode. Neuroimaging and first electroencephalogram (EEG) were normal in all patients. SCN1A gene mutations were detected in 21 (95%) patients. All patients underwent multiple antiepileptic drug (AED) regimens. Psychomotor development was delayed in 20 (91%) patients, and 13 (59%) presented ataxia. At the end of follow-up, the median (IQR) age was 19 (8-23) years, with no reported deaths. Discussion: The characteristics of the first DS seizures are crucial for diagnosis, which can be supported by genetic sequencing, with most patients presenting an SCN1A gene mutation. Neuroimaging and EEG are typically normal at disease onset, but most patients present EEG abnormalities over time. Seizure management can be challenging, requiring a combination of multiple AEDs. Conclusion: DS is a progressive disease associated with poor cognitive and motor skill outcomes, resulting in great morbidity. Early diagnosis can help avoid unnecessary studies, optimize the therapeutic strategy, allow genetic counseling, and improve long-term outcomes.info:eu-repo/semantics/publishedVersio

Mutations in the MECP2 gene are not a major cause of Rett syndrome-like or related neurodevelopmental phenotype in male patients

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified. Thus, additional genes should be screened in this group of patients.Moónica Santos was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal) with the PhD fellowship SFRH/BD/9111/2002 and the postdoc fellowship SFRH/BPD/28555/2006. Research in Rett syndrome is supported by FSE/FEDER and FCT, Grant POCTI 41416/2001

Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR)

Fifty to eighty percent of Rett syndrome (RTT) cases have point mutations in the gene encoding methyl-CpG-binding protein-2 (MECP2). A fraction of MECP2 negative classical RTT patients has large heterozygous deletions. Robust Dosage PCR (RD-PCR) assays were developed as a rapid, convenient and accurate method to detect large heterozygous deletions and duplications. A blinded analysis was performed for 65 RTT cases from Portugal by RDPCR in the coding exons 2-4 of the MECP2 gene. Neither the patients with point mutations nor the non-classical RTT patients without point mutation had a deletion or duplication. One of remaining eight female patients with classical RTT without point mutation had a heterozygous deletion. This is the first report of a deletion spanning the entire MECP2 gene. The deletion was confirmed by southern blotting analysis and the deletion junction was localized 37kb upstream from exon 1 and 18kb downstream from exon 4. No duplications were detected. Our results suggest that RD-PCR is an accurate and convenient molecular diagnostic method

Rett syndrome with and without detected MECP2 mutations: an attempt to redefine phenotypes

Background: The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations. Patients and methods: We analyzed 87 patients fulfilling the clinical criteria for RTT. All were observed and videotaped by the same paediatric neurologist. Seven common mutations were considered separately, and associated clinical features analysed. Results: Comparing Group I and II, we found differences concerning psychomotor development prior to onset, acquisition of propositive manipulation and language, and evolving autistic traits. Based on age at observation, we found differences in eye pointing, microcephaly, growth, number of stereotypies, rigidity, ataxia and ataxic-rigid gait, and severity score. Patients with truncating differed from those with missense mutations regarding acquisition of propositive words and independent gait, before the beginning of the disease, and microcephaly, growth, foot length, dystonia, rigidity and severity score, at the time of observation. Patients with the R168X mutation had a more severe phenotype, whereas those with R133C showed a less severe one. Patients with R294X had a hyperactive behaviour, and those with T158M seemed to be particularly ataxic and rigid. Conclusion: A clear regressive period (with loss of prehension and language, deceleration of growth) and the presence of more than three different stereotypies, rigidity and ataxic-rigid gait seemed to be very helpful in differentiating Group I from Group II

Identification of novel genetic causes of Rett syndrome-like phenotypes

Background The aim of this work was to identify new genetic causes of Rett-like phenotypes using array comparative genomic hybridisation and a whole exome sequencing approach. Methods and results We studied a cohort of 19 Portuguese patients (16 girls, 3 boys) with a clinical presentation significantly overlapping Rett syndrome (RTT). Genetic analysis included filtering of the single nucleotide variants and indels with preference for de novo, homozygous/compound heterozygous, or maternally inherited X linked variants. Examination by MRI and muscle biopsies was also performed. Pathogenic genomic imbalances were found in two patients (10.5%): an 18q21.2 deletion encompassing four exons of the TCF4 gene and a mosaic UPD of chromosome 3. Variants in genes previously implicated in neurodevelopmental disorders (NDD) were identified in six patients (32%): de novo variants in EEF1A2, STXBP1 and ZNF238 were found in three patients, maternally inherited X linked variants in SLC35A2, ZFX and SHROOM4 were detected in two male patients and one homozygous variant in EIF2B2 was detected in one patient. Variants were also detected in five novel NDD candidate genes (26%): we identified de novo variants in the RHOBTB2, SMARCA1 and GABBR2 genes; a homozygous variant in EIF4G1; compound heterozygous variant in HTT. Conclusions Network analysis reveals that these genes interact by means of protein interactions with each other and with the known RTT genes. These findings expand the phenotypical spectrum of previously known NDD genes to encompass RTT-like clinical presentations and identify new candidate genes for RTT-like phenotypes.This work was supported by the Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 262055. This work was also supported by the FEDER through the Programa Operacional Factores de Competitividade-COMPETE and by Portuguese national funds through the FCT-Fundacao para a Ciencia e Tecnologia, grants number PIC/IC/83026/2007 and PIC/IC/83013/2007, PhD scholarship grant to MB number SFRH/BDINT/ 51549/2011 and PhD scholarship grant to FL number SFRH/BD/84650/2010.info:eu-repo/semantics/publishedVersio

Clinical rating scale for pantothenate kinase-associated neurodegeneration: A pilot study

Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration.info:eu-repo/semantics/publishedVersio

Rett syndrome with and without detected MECP2 mutations: An attempt to redefine phenotypes

Abstract Background: The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations. Patients and methods: We analyzed 87 patients fulfilling the clinical criteria for RTT. All were observed and videotaped by the same paediatric neurologist. Seven common mutations were considered separately, and associated clinical features analysed. Results: Comparing Group I and II, we found differences concerning psychomotor development prior to onset, acquisition of propositive manipulation and language, and evolving autistic traits. Based on age at observation, we found differences in eye pointing, microcephaly, growth, number of stereotypies, rigidity, ataxia and ataxic-rigid gait, and severity score. Patients with truncating differed from those with missense mutations regarding acquisition of propositive words and independent gait, before the beginning of the disease, and microcephaly, growth, foot length, dystonia, rigidity and severity score, at the time of observation. Patients with the R168X mutation had a more severe phenotype, whereas those with R133C showed a less severe one. Patients with R294X had a hyperactive behaviour, and those with T158M seemed to be particularly ataxic and rigid. Conclusion: A clear regressive period (with loss of prehension and language, deceleration of growth) and the presence of more than three different stereotypies, rigidity and ataxic-rigid gait seemed to be very helpful in differentiating Group I from Group II