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1.
JAMA ; 325(5): 467-475, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528536

RESUMO

Importance: Cerebral palsy is a common neurodevelopmental disorder affecting movement and posture that often co-occurs with other neurodevelopmental disorders. Individual cases of cerebral palsy are often attributed to birth asphyxia; however, recent studies indicate that asphyxia accounts for less than 10% of cerebral palsy cases. Objective: To determine the molecular diagnostic yield of exome sequencing (prevalence of pathogenic and likely pathogenic variants) in individuals with cerebral palsy. Design, Setting, and Participants: A retrospective cohort study of patients with cerebral palsy that included a clinical laboratory referral cohort with data accrued between 2012 and 2018 and a health care-based cohort with data accrued between 2007 and 2017. Exposures: Exome sequencing with copy number variant detection. Main Outcomes and Measures: The primary outcome was the molecular diagnostic yield of exome sequencing. Results: Among 1345 patients from the clinical laboratory referral cohort, the median age was 8.8 years (interquartile range, 4.4-14.7 years; range, 0.1-66 years) and 601 (45%) were female. Among 181 patients in the health care-based cohort, the median age was 41.9 years (interquartile range, 28.0-59.6 years; range, 4.8-89 years) and 96 (53%) were female. The molecular diagnostic yield of exome sequencing was 32.7% (95% CI, 30.2%-35.2%) in the clinical laboratory referral cohort and 10.5% (95% CI, 6.0%-15.0%) in the health care-based cohort. The molecular diagnostic yield ranged from 11.2% (95% CI, 6.4%-16.2%) for patients without intellectual disability, epilepsy, or autism spectrum disorder to 32.9% (95% CI, 25.7%-40.1%) for patients with all 3 comorbidities. Pathogenic and likely pathogenic variants were identified in 229 genes (29.5% of 1526 patients); 86 genes were mutated in 2 or more patients (20.1% of 1526 patients) and 10 genes with mutations were independently identified in both cohorts (2.9% of 1526 patients). Conclusions and Relevance: Among 2 cohorts of patients with cerebral palsy who underwent exome sequencing, the prevalence of pathogenic and likely pathogenic variants was 32.7% in a cohort that predominantly consisted of pediatric patients and 10.5% in a cohort that predominantly consisted of adult patients. Further research is needed to understand the clinical implications of these findings.


Assuntos
Paralisia Cerebral/genética , Mutação , Sequenciamento Completo do Exoma , Adolescente , Adulto , Paralisia Cerebral/complicações , Criança , Pré-Escolar , Estudos Transversais , Feminino , Testes Genéticos , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/genética , Prevalência , Estudos Retrospectivos
3.
Pediatr Cardiol ; 42(1): 36-41, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33394107

RESUMO

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address (1) developing a risk score to predict adverse outcomes in patients with hypoplastic left heart syndrome using the national pediatric cardiology quality improvement collaborative, (2) outcomes of the Ross procedure in patients with a previous aortic valve surgery showing better outcomes in these patients compared to patients with the primary Ross procedure, (3) the initial experience with continuous flow ventricular assist devices in pediatric patients showing low mortality post implantation, (4) lower socioeconomic status is associated with worse long-term neurodevelopmental outcomes in patients with hypoplastic left heart syndrome, (5) QRS fragmentation is associated with higher incidence of appropriate shock after implantable cardioverter defibrillator implantation in repaired tetralogy of Fallot, (6) atrioventricular valve repair may have better outcomes if performed before the Fontan operation compared to after the Fontan operation.


Assuntos
Cardiologia , Procedimentos Cirúrgicos Cardiovasculares/métodos , Cardiopatias/terapia , Pediatria , Valva Aórtica/cirurgia , Criança , Feminino , Técnica de Fontan/métodos , Cardiopatias/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Coração Auxiliar , Humanos , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Publicações Periódicas como Assunto , Fatores de Risco , Fatores Socioeconômicos , Tetralogia de Fallot/cirurgia
4.
Am J Hum Genet ; 108(2): 346-356, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33513338

RESUMO

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.


Assuntos
Proteínas de Ligação à Região de Interação com a Matriz/genética , Mutação , Transtornos do Neurodesenvolvimento/genética , Cromatina/metabolismo , Feminino , Estudos de Associação Genética , Haploinsuficiência , Humanos , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/química , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Modelos Moleculares , Mutação de Sentido Incorreto , Ligação Proteica , Domínios Proteicos , Transcrição Genética
5.
Nat Rev Mol Cell Biol ; 22(2): 96-118, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33353982

RESUMO

Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA and proteins, lncRNAs can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic mRNAs and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that lncRNAs are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.


Assuntos
Regulação da Expressão Gênica , Doenças do Sistema Imunitário/patologia , Neoplasias/patologia , Transtornos do Neurodesenvolvimento/patologia , RNA Longo não Codificante/genética , Animais , Humanos , Doenças do Sistema Imunitário/genética , Neoplasias/genética , Transtornos do Neurodesenvolvimento/genética , Transdução de Sinais
6.
J Med Internet Res ; 23(1): e22619, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33326409

RESUMO

BACKGROUND: In response to COVID-19, there has been increasing momentum in telehealth development and delivery. To assess the anticipated exponential growth in telehealth, it is important to accurately capture how telehealth has been used in specific mental health fields prior to the pandemic. OBJECTIVE: This systematic review aimed to highlight how telehealth has been used with clinical samples in the neurodevelopmental field, including patients with neurodevelopmental disorders (NDDs), their families, and health care professionals. To identify which technologies show the greatest potential for implementation into health services, we evaluated technologies for effectiveness, economic impact, and readiness for clinical adoption. METHODS: A systematic search of literature was undertaken in April 2018 and updated until December 2019, by using the Medline, Web of Science, Scopus, CINAHL Plus, EMBASE, and PsycInfo databases. Extracted data included the type of technology, how the technology was used (ie, assessment, treatment, and monitoring), participant characteristics, reported outcomes and authors' views on clinical effectiveness, user impact (ie, feasibility and acceptability), economic impact, and readiness for clinic adoption. A quality review of the research was performed in accordance with the Oxford Centre for Evidence-Based Medicine Levels of Evidence. RESULTS: A total of 42 studies met the inclusion criteria. These studies included participants and family members with autism spectrum disorders (21/42, 50%), attention deficit hyperactivity disorders (8/42, 19%), attention deficit hyperactivity or autism spectrum disorders (3/42, 7%), communication disorders (7/42, 17%), and tic disorders (2/42, 5%). The focus of most studies (33/42, 79%) was on treatment, rather than assessment (4/42, 10%) or monitoring (5/42, 12%). Telehealth services demonstrated promise for being clinically effective, predominantly in relation to diagnosing and monitoring NDDs. In terms of NDD treatment, telehealth services were usually equivalent to control groups. There was some evidence of positive user and economic impacts, including increased service delivery efficiency (eg, increased treatment availability and decreased waiting times). However, these factors were not widely recorded across the studies. Telehealth was demonstrated to be cost-effective in the few studies that considered cost-effectiveness. Study quality varied, as many studies had small sample sizes and inadequate control groups. Of the 42 studies, only 11 (26%) were randomized controlled trials, 12 (29%) were case studies or case series, 6 (14%) were qualitative studies, and 5 (12%) were noncomparative trials. CONCLUSIONS: Telehealth has the potential to increase treatment availability, decrease diagnosis waiting times, and aid in NDD monitoring. Further research with more robust and adequately powered study designs that consider cost-effectiveness and increased efficiency is needed. This systematic review highlights the extent of telehealth technology use prior to the COVID-19 pandemic and the movement for investing in remote access to treatments. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42018091156; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018091156.


Assuntos
Monitorização Fisiológica/métodos , Transtornos do Neurodesenvolvimento/terapia , Telemedicina/métodos , Feminino , Humanos , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Pesquisa Qualitativa
8.
Am J Hum Genet ; 108(1): 148-162, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33308442

RESUMO

SYNGAP1 is a neuronal Ras and Rap GTPase-activating protein with important roles in regulating excitatory synaptic plasticity. While many SYNGAP1 missense and nonsense mutations have been associated with intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder (ASD), whether and how they contribute to individual disease phenotypes is often unknown. Here, we characterize 57 variants in seven assays that examine multiple aspects of SYNGAP1 function. Specifically, we used multiplex phospho-flow cytometry to measure variant impact on protein stability, pERK, pGSK3ß, pp38, pCREB, and high-content imaging to examine subcellular localization. We find variants ranging from complete loss-of-function (LoF) to wild-type (WT)-like in their regulation of pERK and pGSK3ß, while all variants retain at least partial ability to dephosphorylate pCREB. Interestingly, our assays reveal that a larger proportion of variants located within the disordered domain of unknown function (DUF) comprising the C-terminal half of SYNGAP1 exhibited higher LoF, compared to variants within the better studied catalytic domain. Moreover, we find protein instability to be a major contributor to dysfunction for only two missense variants, both located within the catalytic domain. Using high-content imaging, we find variants located within the C2 domain known to mediate membrane lipid interactions exhibit significantly larger cytoplasmic speckles than WT SYNGAP1. Moreover, this subcellular phenotype shows both correlation with altered catalytic activity and unique deviation from signaling assay results, highlighting multiple independent molecular mechanisms underlying variant dysfunction. Our multidimensional dataset allows clustering of variants based on functional phenotypes and provides high-confidence, multi-functional measures for making pathogenicity predictions.


Assuntos
GTP Fosfo-Hidrolases/genética , Mutação/genética , Transdução de Sinais/genética , Proteínas Ativadoras de ras GTPase/genética , Transtorno do Espectro Autista/genética , Linhagem Celular , Epilepsia/genética , Células HEK293 , Humanos , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Estabilidade Proteica
9.
Am J Hum Genet ; 108(1): 134-147, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33340455

RESUMO

The ubiquitin-proteasome system facilitates the degradation of unstable or damaged proteins. UBR1-7, which are members of hundreds of E3 ubiquitin ligases, recognize and regulate the half-life of specific proteins on the basis of their N-terminal sequences ("N-end rule"). In seven individuals with intellectual disability, epilepsy, ptosis, hypothyroidism, and genital anomalies, we uncovered bi-allelic variants in UBR7. Their phenotype differs significantly from that of Johanson-Blizzard syndrome (JBS), which is caused by bi-allelic variants in UBR1, notably by the presence of epilepsy and the absence of exocrine pancreatic insufficiency and hypoplasia of nasal alae. While the mechanistic etiology of JBS remains uncertain, mutation of both Ubr1 and Ubr2 in the mouse or of the C. elegans UBR5 ortholog results in Notch signaling defects. Consistent with a potential role in Notch signaling, C. elegans ubr-7 expression partially overlaps with that of ubr-5, including in neurons, as well as the distal tip cell that plays a crucial role in signaling to germline stem cells via the Notch signaling pathway. Analysis of ubr-5 and ubr-7 single mutants and double mutants revealed genetic interactions with the Notch receptor gene glp-1 that influenced development and embryo formation. Collectively, our findings further implicate the UBR protein family and the Notch signaling pathway in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism that differs from JBS. Further studies exploring a potential role in histone regulation are warranted given clinical overlap with KAT6B disorders and the interaction of UBR7 and UBR5 with histones.


Assuntos
Epilepsia/genética , Hipotireoidismo/genética , Transtornos do Neurodesenvolvimento/genética , Receptores Notch/genética , Transdução de Sinais/genética , Ubiquitina-Proteína Ligases/genética , Animais , Anus Imperfurado/genética , Caenorhabditis elegans/genética , Linhagem Celular , Displasia Ectodérmica/genética , Transtornos do Crescimento/genética , Células HEK293 , Perda Auditiva Neurossensorial/genética , Histonas/genética , Humanos , Deficiência Intelectual/genética , Camundongos , Mutação/genética , Nariz/anormalidades , Pancreatopatias/genética , Complexo de Endopeptidases do Proteassoma/genética
10.
Res Dev Disabil ; 109: 103840, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33383468

RESUMO

Research on the psychological impact of the COVID-19 pandemic highlighted negative effects on the general population and particularly on parents. However, little is known about families of children with Neurodevelopmental Disorder (NDD). The present study investigated parental stress, coparenting, and child adjustment in Italian families with children with NDD (N = 82) and typical developing children (TD, N = 82) during lockdown, using an online survey. Results of quantitative analyses showed a significant increase in parental stress and child externalizing behaviors, but not of coparenting. Parental stress is predicted by externalizing behaviors, and coparenting acted as a moderator in the relationship between the change in the amount of time spent with the children before and during lockdown and parental stress. In children with NDD, the decrease in therapeutic/rehabilitation support predicted higher externalizing behaviors. Qualitative analysis showed that beyond the difficulties and worries arising during lockdown, most of the parents appreciated the opportunity of spending more time with their children and strengthening the parent-child relationship. In conclusion, our results point out the importance of ensuring continuity of care for children with NDD (e.g. telehealth) during home confinement and of providing psychological support for parents.


Assuntos
Controle de Doenças Transmissíveis/métodos , Transtornos do Neurodesenvolvimento , Pais/psicologia , Comportamento Problema/psicologia , Estresse Psicológico , Adaptação Psicológica , Adulto , /prevenção & controle , Criança , Comportamento Infantil , Feminino , Humanos , Itália/epidemiologia , Masculino , Determinação de Necessidades de Cuidados de Saúde , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/psicologia , Sistemas de Apoio Psicossocial , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controle , Inquéritos e Questionários , Telemedicina/métodos
11.
Pediatr Cardiol ; 42(1): 1-18, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33373013

RESUMO

Congenital heart defects (CHD) is one of the most common types of birth defects. Thanks to advances in surgical techniques and intensive care, the majority of children with severe forms of CHD survive into adulthood. However, this increase in survival comes with a cost. CHD survivors have neurological functioning at the bottom of the normal range. A large spectrum of central nervous system dysmaturation leads to the deficits seen in critical CHD. The heart develops early during gestation, and CHD has a profound effect on fetal brain development for the remainder of gestation. Term infants with critical CHD are born with an immature brain, which is highly susceptible to hypoxic-ischemic injuries. Perioperative blood flow disturbances due to the CHD and the use of cardiopulmonary bypass or circulatory arrest during surgery cause additional neurological injuries. Innate patient factors, such as genetic syndromes and preterm birth, and postoperative complications play a larger role in neurological injury than perioperative factors. Strategies to reduce the disability burden in critical CHD survivors are urgently needed.


Assuntos
Encefalopatias/epidemiologia , Cardiopatias Congênitas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Encéfalo/crescimento & desenvolvimento , Lesões Encefálicas/epidemiologia , Ponte Cardiopulmonar/métodos , Criança , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Hipóxia-Isquemia Encefálica/epidemiologia , Lactente , Recém-Nascido , Transtornos do Neurodesenvolvimento/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Sobreviventes
13.
N Engl J Med ; 383(27): 2639-2651, 2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-33382931

RESUMO

BACKGROUND: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. METHODS: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. RESULTS: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. CONCLUSIONS: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).


Assuntos
Anemia/terapia , Transfusão de Eritrócitos , Hemoglobinas/análise , Recém-Nascido de Peso Extremamente Baixo ao Nascer/sangue , Lactente Extremamente Prematuro/sangue , Doenças do Prematuro/terapia , Transtornos do Neurodesenvolvimento/prevenção & controle , Algoritmos , Anemia/sangue , Anemia/mortalidade , Paralisia Cerebral/prevenção & controle , Transtornos Cognitivos/prevenção & controle , Transfusão de Eritrócitos/efeitos adversos , Perda Auditiva/prevenção & controle , Humanos , Recém-Nascido/sangue , Recém-Nascido Prematuro/sangue , Doenças do Prematuro/sangue , Doenças do Prematuro/mortalidade , Taxa de Sobrevida , Transtornos da Visão/prevenção & controle
14.
Cochrane Database Syst Rev ; 12: CD013309, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33348448

RESUMO

BACKGROUND: Preterm infants are susceptible to hyperglycemia and hypoglycemia, conditions which may lead to adverse neurodevelopment. The use of continuous glucose monitoring devices (CGM) might help keeping glucose levels in the normal range, and reduce the need for blood sampling. However, the use of CGM might be associated with harms in the preterm infant. OBJECTIVES: Objective one: to assess the benefits and harms of CGM alone versus standard method of glycemic measure in preterm infants. Objective two: to assess the benefits and harms of CGM with automated algorithm versus standard method of glycemic measure in preterm infants. Objective three: to assess the benefits and harms of CGM with automated algorithm versus CGM without automated algorithm in preterm infants. SEARCH METHODS: We adopted the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 9), in the Cochrane Library; MEDLINE via PubMed (1966 to 25 September 2020); Embase (1980 to 25 September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 25 September 2020). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs in preterm infants comparing: 1) the use of CGM versus intermittent modalities to measure glycemia (comparison 1); or CGM associated with prespecified interventions to correct hypoglycemia or hyperglycemia versus CGM without such prespecified interventions (comparison 2). DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: Four trials enrolling 138 infants met our inclusion criteria. Investigators in three trials (118 infants) compared the use of CGM to intermittent modalities (comparison one); however one of these trials was analyzed separately because CGM was used as a standalone device, without being coupled to a control algorithm like in the other trials. A fourth trial (20 infants) assessed CGM with an automated algorithm versus CGM with a manual algorithm. None of the four included trials reported the neurodevelopmental outcome, i.e. the primary outcome of this review. Within comparison one, the certainty of the evidence on the use of CGM on mortality during hospitalization is very uncertain (typical RR 3.00, 95% CI 0.13 to 70.30; typical RD 0.04, 95% CI -0.06 to 0.14; 50 participants; 1  study; very low certainty). The number of hypoglycemic episodes was reported in two studies with conflicting data. The number of hyperglycemic episodes was reported in one study (typical MD -1.40, 95% CI -2.84 to 0.04; 50 participants; 1 study). The certainty of the evidence was very low for all outcomes because of limitations in study design, and imprecision of estimates.  Three studies are ongoing. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine if CGM improves preterm infant mortality or morbidities. Long-term outcomes were not reported. Clinical trials are required to determine the most effective CGM and glycemic management regimens in preterm infants before larger studies can be performed to assess the efficacy of CGM  for reducing mortality, morbidity and long-term neurodevelopmental impairments. The absence of CGM labelled for neonatal use is still a major limit in its use as well as the absence of dedicated neonatal devices.


Assuntos
Algoritmos , Glicemia/análise , Hiperglicemia/diagnóstico , Hipoglicemia/diagnóstico , Recém-Nascido Prematuro/sangue , Viés , Técnicas Biossensoriais/instrumentação , Mortalidade Hospitalar , Humanos , Hiperglicemia/epidemiologia , Hipoglicemia/epidemiologia , Lactente , Mortalidade Infantil , Recém-Nascido , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Transtornos do Neurodesenvolvimento , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Artigo em Inglês | MEDLINE | ID: mdl-33321999

RESUMO

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.


Assuntos
Variações do Número de Cópias de DNA , Transtornos Mentais/genética , Transtornos do Neurodesenvolvimento/genética , Deleção Cromossômica , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Heterozigoto , Humanos
17.
Rev. cuba. pediatr ; 92(4): e918, oct.-dic. 2020. tab, graf
Artigo em Inglês | LILACS, CUMED | ID: biblio-1144519

RESUMO

Introduction: Neurodevelopmental disorders (NDD) are featured by a delay in the acquisition of motor functions, cognitive abilities and speech, or combined deficits in these areas with the onset before the age of 5 years. Genetic causes account for approximately a half of all NDD cases. Objective: to describe alterations of the genome implied in neurodevelopmental disorders and some aspects of their genetic counseling. Methods: Bibliographic search in Medline, Pubmed, Scielo, LILACS and Cochrane, emphasizing in the last five years, the relationship between the various genetic factors that may be involved in neurodevelopmental disorders. Results: Multiple genetic factors are involved in neurodevelopmental disorders, from gross ones such as chromosomal aneuploidies to more subtle ones such as variations in the number of copies in the genome. Special emphasis is placed on microdeletion-micro duplication syndromes as a relatively frequent cause of NDDs and their probable mechanisms of formation are explained. Final Considerations: Genetic aberrations are found in at least 30-50 percent of children with NDD. Conventional karyotyping allows the detection of chromosomal aberrations encompassing more than 5-7 Mb, which represent 5-10 percent of causative genome rearrangements in NDD. Molecular karyotyping (e.g. SNP array/array CGH) can significantly improve the yield in patients with NDD and congenital malformations(AU)


Introducción: Los trastornos del neurodesarrollo están caracterizados por retardo en la adquisición de las funciones motoras, habilidades cognitivas para el habla o el déficit combinado en estas áreas; se presenta en niños menores de 5 años de edad. Las causas genéticas están implicadas en más de la mitad de los pacientes con estos trastornos Objetivo: Examinar las alteraciones del genoma implicados en los trastornos del neurodesarrollo y algunos aspectos de su asesoramiento genético. Métodos: Búsqueda bibliográfica en Medline, Pubmed, Scielo, LILACS y Cochrane con énfasis en los últimos cinco años, acerca de la relación entre los variados factores genéticos que pueden estar involucrados en los trastornos del neurodesarrollo. Resultados: Los factores genéticos involucrados pueden ser groseros como las aneuploidías cromosómicas hasta los más sutiles como las variaciones en el número de copias en el genoma. Se describen los síndromes de microdeleción-micro duplicación como una causa relativamente frecuente de los trastornos del neurodesarrollo y se explican sus probables mecanismos de formación. Se relacionan las aneuploidías cromosómicas y las variaciones en el número de copia como causas de estos trastornos. Consideraciones finales . Las aberraciones genéticas se encuentran en 30-50 por ciento de los niños con trastornos del neurodesarrollo. El cariotipo convencional permite la detección de aberraciones cromosómicas que abarcan más de 5-7 Mb, lo que representa 5-10 por ciento de los reordenamientos genómicos causales en estos trastornos. El cariotipo molecular (por ejemplo, una matriz de SNP/ CGH de matriz) puede mejorar significativamente la certeza del diagnóstico en pacientes con trastornos del neurodesarrollo y malformaciones congénitas(AU)


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Aberrações Cromossômicas , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/epidemiologia , Genoma Humano/genética
18.
Rev. neurol. (Ed. impr.) ; 71(10): 365-372, 16 nov., 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-ET6-1307

RESUMO

INTRODUCCIÓN: El estado epiléptico representa la emergencia neurológica más frecuente en pediatría. Las convulsiones febriles prolongadas representan la etiología más frecuente. Nuestro objetivo es actualizar su epidemiología y analizar sus consecuencias evolutivas. PACIENTES Y MÉTODOS: Estudio observacional analítico de cohortes retrospectivas de niños atendidos en urgencias con estado epiléptico entre enero de 2014 y diciembre de 2018. Se recogieron las variables demográficas, los antecedentes personales, las características clínicas, las pruebas complementarias y la etiología de los estados epilépticos seguidos en nuestro hospital. Se analizaron las consecuencias evolutivas en cuanto a neurodesarrollo y epilepsia ulterior. RESULTADOS: De un total de 525.000 urgencias atendidas durante el estudio, los casos de estado epiléptico fueron 79 en 68 pacientes (16 casos/100.000 niños/año). La etiología sintomática fue la más frecuente (35,4%). El 20,6% de los pacientes presentaba antecedente de prematuridad; el 30,8%, un déficit del neurodesarrollo previo, más frecuente en caso de etiología sintomática, y el 44% estaba diagnosticado de epilepsia. La duración mediana de las crisis fue de 50 minutos. En siete pacientes se identificó un desencadenante cerebral agudo. El déficit del neurodesarrollo ulterior achacable al estado epiléptico fue del 9,1%, y se relacionó con la etiología sintomática o antecedentes de prematuridad. El desarrollo de epilepsia ocurrió en el 10,7%. CONCLUSIONES: La alteración del neurodesarrollo achacable al estado epiléptico afecta a uno de cada 11 casos. La prematuridad fue un factor de riesgo por sí misma. La epilepsia posterior a un estado epiléptico se desarrolló en uno de cada 10 casos


INTRODUCTION: Epileptic status represents the most frequent neurological emergency in pediatrics. Prolonged febrile seizures represent the most common etiology. Our objective is to update its epidemiology and analyze its evolutionary consequences. PATIENTS AND METHODS: Observational analytical study of retrospective cohorts of children seen in the emergency department with epileptic status between January-2014 and December-2018. Demographic variables, personal history, clinical characteristics, complementary tests and the etiology of the epileptic status followed in our hospital were collected. The evolutionary consequences in terms of neurodevelopment and subsequent epilepsy were analyzed. RESULTS: Of a total of 525,000 emergencies attended during the study, epileptic status cases were 79 in 68 patients (16 cases/100,000 children/year). The symptomatic etiology was the most frequent (35.4%). 20.6% of the patients had a history of prematurity, 30.8% had a deficit of previous neurodevelopment, this being more frequent in case of symptomatic etiology, and 44% were diagnosed with epilepsy. The median duration of seizures was 50 minutes. An acute brain trigger was identified in seven patients. The subsequent neurodevelopmental deficit attributable to epileptic status was 9.1% of patients related to symptomatic etiology and/or a history of prematurity. The development of epilepsy occurred in 10.7%. CONCLUSIONS: The neurodevelopmental disorder attributable to epileptic status affects one in 11 cases. Prematurity was a risk factor per se. Post-epileptic status epilepsy developed in one in 10 cases


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Estado Epiléptico/epidemiologia , Estado Epiléptico/fisiopatologia , Convulsões Febris/epidemiologia , Convulsões Febris/fisiopatologia , Estado Epiléptico/etiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/epidemiologia , Estudos Retrospectivos , Prognóstico , Fatores de Risco , Espanha/epidemiologia
19.
Nat Commun ; 11(1): 5236, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067431

RESUMO

The etiology of major neurodevelopmental disorders such as schizophrenia and autism is unclear, with evidence supporting a combination of genetic factors and environmental insults, including viral infection during pregnancy. Here we utilized a mouse model of maternal immune activation (MIA) with the viral mimic PolyI:C infection during early gestation. We investigated the transcriptional changes in the brains of mouse fetuses following MIA during the prenatal period, and evaluated the behavioral and biochemical changes in the adult brain. The results reveal an increase in RNA editing levels and dysregulation in brain development-related gene pathways in the fetal brains of MIA mice. These MIA-induced brain editing changes are not observed in adulthood, although MIA-induced behavioral deficits are observed. Taken together, our findings suggest that MIA induces transient dysregulation of RNA editing at a critical time in brain development.


Assuntos
Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/genética , Complicações na Gravidez/imunologia , Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/genética , Edição de RNA , Animais , Comportamento Animal , Encéfalo/crescimento & desenvolvimento , Encéfalo/imunologia , Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Imunidade Materno-Adquirida , Camundongos , Camundongos Endogâmicos C57BL , Transtornos do Neurodesenvolvimento/imunologia , Transtornos do Neurodesenvolvimento/psicologia , Poli I-C/efeitos adversos , Poli I-C/imunologia , Complicações na Gravidez/etiologia , Complicações na Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
20.
Child Adolesc Ment Health ; 25(4): 265-266, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33049100

RESUMO

The COVID-19 pandemic lockdown response has had a disproportionate and damaging effect on the lives, mental health and well-being of young people globally. They have been neglected in policy-making and their needs have been subjugated to those of adults which contravenes the UN Convention on the Rights of the Child. Here, I argue that the needs and rights of young people must come first to protect their health, mental health and futures. If we do not do this, we will let down a generation of children who will bear the brunt of the fallout of the economic burden of the global COVID-19 crisis.


Assuntos
Infecções por Coronavirus , Saúde Mental , Pandemias , Pneumonia Viral , Quarentena/psicologia , Instituições Acadêmicas/organização & administração , Estudantes/psicologia , Adolescente , Criança , Humanos , Aprendizagem , Transtornos do Neurodesenvolvimento/psicologia
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