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1.
Rev Med Liege ; 75(10): 686-691, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-33030847

RESUMO

Global developmental delay (GDD) and intellectual development disorder (IDD) are common but heterogeneous pediatric conditions. Guided by a rigorous clinical and anamnestic examination, the diagnostic approach is a dynamic process which is not limited to the intelligence quotient measurement. A large panel of paraclinical tests allows etiological exploration; this generally includes biological, genetic, metabolic and iconographic examinations. To maximize therapeutic efficiency and standardize practices, this document provides a guideline for the management of pediatric GDD/IDD.


Assuntos
Deficiências do Desenvolvimento , Deficiência Intelectual , Criança , Cognição , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Família , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etiologia
2.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32817440

RESUMO

OBJECTIVES: To assess the relation between exposure to maternal depression before age 5 and 5 domains of developmental vulnerability at school entry, overall, and by age at exposure. METHODS: This cohort study included all children born in Manitoba, Canada, who completed the Early Development Instrument between 2005 and 2016 (N = 52 103). Maternal depression was defined by using physician visits, hospitalizations, and pharmaceutical data; developmental vulnerability was assessed by using the Early Development Instrument. Relative risk of developmental vulnerability was assessed by using log-binomial regression models adjusted for characteristics at birth. RESULTS: Children exposed to maternal depression before age 5 had a 17% higher risk of having at least 1 developmental vulnerability at school entry than did children not exposed to maternal depression before age 5. Exposure to maternal depression was most strongly associated with difficulties in social competence (adjusted relative risk [aRR] = 1.28; 95% confidence interval [CI]: 1.20-1.38), physical health and well-being (aRR = 1.28; 95% CI: 1.20-1.36), and emotional maturity (aRR = 1.27; 95% CI: 1.18-1.37). For most developmental domains, exposure to maternal depression before age 1 and between ages 4 and 5 had the strongest association with developmental vulnerability. CONCLUSIONS: Our finding that children exposed to maternal depression are at higher risk for developmental vulnerability at school entry is consistent with previous findings. We extended this literature by documenting that the adverse effects of exposure to maternal depression are specific to particular developmental domains and that these effects vary depending on the age at which the child is exposed to maternal depression.


Assuntos
Depressão/complicações , Deficiências do Desenvolvimento/etiologia , Nível de Saúde , Mães/psicologia , Habilidades Sociais , Pré-Escolar , Estudos de Coortes , Intervalos de Confiança , Depressão/diagnóstico , Depressão/epidemiologia , Depressão Pós-Parto/complicações , Feminino , Humanos , Lactente , Manitoba/epidemiologia , Risco , Irmãos/psicologia , Fatores Socioeconômicos , Adulto Jovem
5.
Zhonghua Er Ke Za Zhi ; 58(6): 493-498, 2020 Jun 02.
Artigo em Chinês | MEDLINE | ID: mdl-32521962

RESUMO

Objective: To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation. Methods: The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively. Results: Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038_1039delCC, c.348_351dupTGAA. Conclusions: Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.


Assuntos
Encefalopatias/diagnóstico por imagem , Encefalopatias/genética , Eletroencefalografia , Epilepsia/genética , Proteínas Munc18/genética , Espasmos Infantis/genética , Encefalopatias/diagnóstico , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Epilepsia/etiologia , Feminino , Humanos , Lactente , Masculino , Mutação , Mutação Puntual , Estudos Retrospectivos , Espasmos Infantis/etiologia
7.
PLoS One ; 15(6): e0233949, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479548

RESUMO

BACKGROUND: Undernutrition leads to impaired psychosocial and cognitive development. This study explored the developmental status of children with complicated severe acute malnutrition (SAM) and correlated it with various risk factors for SAM. METHODS AND FINDINGS: We recruited 100 children with SAM and no other associated significant health issues during the recovery phase of treatment using the Bayley Scales of Infant and Toddler Development III prior to discharge from the nutritional rehabilitation unit in R D Gardi Medical College, Ujjain, Central India. We also assessed composite developmental scores, developmental age equivalents, and average differences in developmental age. Risk factors for developmental delay were identified in children with complicated SAM. The results revealed that 75%, 75%, and 63% of children with SAM exhibited delay in motor (mean score: 78.22), language (mean score: 83.97), and cognitive (mean score: 78.06) domains, respectively. A total of 63% children exhibited delay by an average of 4-7 months in the total developmental age. The proportion of children with delay in motor, language, and cognitive domains was determined. An increased risk of global developmental delay was observedin children with a low birth weight (adjusted odds ratio [aOR]: 18.06, 95%CI: 2.08-156.56; P = 0.009), having working mothers (aOR: 17.54, 95%CI: 3.02-102.59; P = 0.001), weight-for-age less than three standard deviations (aOR: 6.09, 95%CI: 1.08-34.10; P = 0.04), and presence of severe anemia (aOR: 16.34, 95%CI: 2.94-90.73; P = 0.001). CONCLUSIONS: The results indicated that children with SAM exhibit developmental delay across all domains. Identifying multiple modifiable risk factors for developmental delay in children with SAM will be helpful in devising early interventional strategies in low-middle income countries; however, the exact timing of such interventions should be investigated.


Assuntos
Desenvolvimento Infantil/fisiologia , Deficiências do Desenvolvimento/epidemiologia , Comportamento Alimentar/fisiologia , Desnutrição Aguda Grave/complicações , Pré-Escolar , Estudos Transversais , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Idioma , Masculino , Alta do Paciente , Fatores de Risco , Desnutrição Aguda Grave/reabilitação
8.
Neurology ; 95(6): e718-e732, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32518148

RESUMO

OBJECTIVE: To characterize the extent of CNS involvement in children with Pompe disease using brain MRI and developmental assessments. METHODS: The study included 14 children (ages 6-18 years) with infantile Pompe disease (IPD) (n = 12) or late-onset Pompe disease (LOPD) (n = 2) receiving enzyme replacement therapy. White matter (WM) hyperintense foci seen in the brain MRIs were systematically quantified using the Fazekas scale (FS) grading system with a novel approach: the individual FS scores from 10 anatomical areas were summed to yield a total FS score (range absent [0] to severe [30]) for each child. The FS scores were compared to developmental assessments of cognition and language obtained during the same time period. RESULTS: Mild to severe WM hyperintense foci were seen in 10/12 children with IPD (median age 10.6 years) with total FS scores ranging from 2 to 23. Periventricular, subcortical, and deep WM were involved. WM hyperintense foci were seen throughout the path of the corticospinal tracts in the brain in children with IPD. Two children with IPD had no WM hyperintense foci. Children with IPD had relative weaknesses in processing speed, fluid reasoning, visual perception, and receptive vocabulary. The 2 children with LOPD had no WM hyperintense foci, and high scores on most developmental assessments. CONCLUSION: This study systematically characterized WM hyperintense foci in children with IPD, which could serve as a benchmark for longitudinal follow-up of WM abnormalities in patients with Pompe disease and other known neurodegenerative disorders or leukodystrophies in children.


Assuntos
Encefalopatias Metabólicas Congênitas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Doença de Depósito de Glicogênio Tipo II/diagnóstico por imagem , Imagem por Ressonância Magnética , Neuroimagem , Adolescente , Idade de Início , Encéfalo/patologia , Encefalopatias Metabólicas Congênitas/etiologia , Criança , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Estudos Transversais , Deficiências do Desenvolvimento/etiologia , Terapia de Reposição de Enzimas , Glucana 1,4-alfa-Glucosidase/uso terapêutico , Doença de Depósito de Glicogênio Tipo II/complicações , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Doença de Depósito de Glicogênio Tipo II/psicologia , Humanos , Transtornos da Linguagem/diagnóstico por imagem , Transtornos da Linguagem/etiologia , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Substância Branca/diagnóstico por imagem
9.
PLoS Negl Trop Dis ; 14(5): e0008328, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32407313

RESUMO

The dual burden of enteric infection and childhood malnutrition continues to be a global health concern and a leading cause of morbidity and death among children. Campylobacter infection, in particular, is highly prevalent in low- and middle-income countries, including Bangladesh. We examined longitudinal data to evaluate the trajectories of change in child growth, and to identify associations with Campylobacter infection and household factors. The study analyzed data from 265 children participating in the MAL-ED Study in Mirpur, Bangladesh. We applied latent growth curve modelling to evaluate the trajectories of change in children's height, as measured by length-for-age z-score (LAZ), from age 0-24 months. Asymptomatic and symptomatic Campylobacter infections were included as 3- and 6-month lagged time-varying covariates, while household risk factors were included as time-invariant covariates. Maternal height and birth order were positively associated with LAZ at birth. An inverse association was found between increasing age and LAZ. Campylobacter infection prevalence increased with age, with over 70% of children 18-24 months of age testing positive for infection. In the final model, Campylobacter infection in the preceding 3-month interval was negatively associated with LAZ at 12, 15, and 18 months of age; similarly, infection in the preceding 6-month interval was negatively associated with LAZ at 15, 18, and 21 months of age. Duration of antibiotic use and access to treated drinking water were negatively associated with Campylobacter infection, with the strength of the latter effect increasing with children's age. Campylobacter infection had a significant negative effect on child's growth and this effect was most powerful between 12 and 21 months. The treatment of drinking water and increased antibiotic use have a positive indirect effect on linear child growth trajectory, acting via their association with Campylobacter infection.


Assuntos
Infecções por Campylobacter/epidemiologia , Deficiências do Desenvolvimento/etiologia , Características da Família , Desnutrição/epidemiologia , Adolescente , Adulto , Antropometria , Bangladesh/epidemiologia , Bioestatística , Infecções por Campylobacter/complicações , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Desnutrição/complicações , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
10.
Plast Reconstr Surg ; 145(5): 1241-1248, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32332546

RESUMO

BACKGROUND: Reports of neurodevelopmental delays in adolescents with metopic craniosynostosis have ranged from 15 to 61 percent. Previously, event-related potentials have correlated preoperative radiographic severity with language deficiencies in infancy. This study sought to characterize neurocognitive testing at cranial maturity and correlate outcomes to preoperative radiographic severity. METHODS: Patients diagnosed with metopic craniosynostosis who underwent surgical correction in infancy completed a neurodevelopmental battery evaluating age-normalized intelligence quotient, academic achievement, and visuomotor integration. Data were stratified by preoperative endocranial bifrontal angle (moderate, >124 degrees; severe, <124 degrees). Multiple variable regression was used to control measured intelligence and achievement for age at surgery, age at testing, parental education, and income. Significance was set at p < 0.05. RESULTS: Twenty patients completed neurodevelopmental testing. Mean intelligence quotient was 111.7 ± 13 and academic achievement was similar to national averages (word reading, 53.4 percent; reading comprehension, 53.4 percent; reading composite, 53.5 percent; spelling, 44 percent; and math, 52.9 percent). Radiographic measurements revealed 36 percent of patients with moderate phenotype and 64 percent with severe. Patients with severe phenotypes had lower intelligence quotient measures and scored more poorly in every academic measure tested. Word reading (113 versus 95; p = 0.035) and reading composite (109 versus 98; p = 0.014) reached significance. CONCLUSIONS: Overall, cranial mature patients with metopic craniosynostosis had above average intelligence quotient and academic achievement near the national mean. Long-term neurocognitive function was correlated to preoperative radiographic severity in metopic craniosynostosis, with more severe cases performing worse. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Sucesso Acadêmico , Craniossinostoses/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Procedimentos Cirúrgicos Reconstrutivos , Crânio/diagnóstico por imagem , Adolescente , Criança , Craniossinostoses/complicações , Craniossinostoses/cirurgia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/prevenção & controle , Feminino , Humanos , Lactente , Testes de Inteligência , Masculino , Período Pré-Operatório , Radiografia , Índice de Gravidade de Doença , Resultado do Tratamento
11.
Am J Trop Med Hyg ; 102(5): 955-963, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32228785

RESUMO

Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraíba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention.


Assuntos
Desenvolvimento Infantil , Infecção por Zika virus/congênito , Adolescente , Adulto , Fatores Etários , Brasil/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/virologia , Surtos de Doenças , Feminino , Seguimentos , Audição , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Microcefalia/virologia , Desempenho Psicomotor , Visão Ocular , Adulto Jovem , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia
14.
Rev. Rol enferm ; 43(3): 169-183, mar. 2020. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193818

RESUMO

INTRODUCCIÓN: La supervivencia de cáncer infantil a los 5 años está aumentando gracias a los tratamientos existentes; no obstante, los efectos de esta enfermedad y su tratamiento siguen causando grandes afectaciones en todo el organismo. OBJETIVOS: Conocer cómo afecta la quimioterapia y radioterapia al crecimiento y desarrollo del niño a corto y largo plazo. Identificar si en el seguimiento enfermero pediátrico se tienen en cuenta los efectos de este tratamiento en la valoración del niño. METODOLOGÍA: Tipo de estudio: Revisión bibliográfica. Bases de datos: PUBMED, CINAHL, CUIDATGE y CUIDEN. Para una estrategia de búsqueda exhaustiva se utilizó la combinación de filtros (artículos de los últimos 6 años, idioma español o inglés), truncamientos, operadores lógicos, subtemas y thesaurus. RESULTADOS: Se obtuvieron 29 referencias. Estas se clasificaron en función de los sistemas corporales afectados por el tratamiento y del desarrollo y crecimiento en la edad pediátrica. Se añadió una segunda clasificación en función del método de seguimiento utilizado por las enfermeras. DISCUSIÓN: El análisis de los resultados aporta grandes similitudes y diferencias entre autores, así como en el seguimiento enfermero de los pacientes pediátricos con cáncer, la confrontación ética y legal en la conservación de gónadas y diferencias por edad y sexo. CONCLUSIONES: Actualmente el papel de la enfermera oncológica pediátrica tiene gran importancia por los cuidados proporcionados. Pero existe poca evidencia respecto el seguimiento de los efectos del tratamiento, por lo que es necesario seguir realizando investigación e incrementar conocimiento para reducir complicaciones


INTRODUCTION: Childhood cancer survival at five years old is increasing thanks to existing treatments. However, the effects of this disease and its treatment are still causing major effects throughout the body. OBJECTIVES: Know how chemotherapy and radiotherapy affect growth and development of child in short and long term. Identify if in the pediatric nursing monitoring the effects of this treatments are taken into account in the assessment of the child. METHOD: Type of study: Review of the literature. Databases: PUBMED, CINAHL, CUIDATGE and CUIDEN. The combination of filters (articles from the last 6 years, Spanish or English language), truncation, logical operators, sub themes and thesaurus were used for a thorough search strategy. RESULTS. Twenty-nine references were found. These were classified according to the body systems affected by the treatment, the development and growth in the pediatric age. A second classification was added depending on the monitoring method used by the nurses. CONCLUSIONS: Oncology pediatric nurse paper has a great importance for the care provided at present. There is little evidence in relation to the monitoring of treatment effects so it is necessary to continue making research and increasing knowledge to minimize complications


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Radioterapia/efeitos adversos , Antineoplásicos/efeitos adversos , Deficiências do Desenvolvimento/etiologia , Insuficiência de Crescimento/etiologia , Enfermagem Oncológica , Enfermagem Pediátrica , Cuidados de Enfermagem , Seguimentos
15.
PLoS One ; 15(3): e0230678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196539

RESUMO

PURPOSE: The purpose of this study was to evaluate neurodevelopmental outcomes in 18-month old (corrected age) preterm infants who received an intravitreal bevacizumab (IVB) injection for the treatment of type 1 retinopathy of prematurity (ROP). METHODS: In this ten-year retrospective study, we reviewed the medical records of patients who underwent ROP screening at Kyushu University Hospital. Among the patients who received IVB or laser photocoagulation (LPC) for the treatment of type 1 ROP, we included infants whose neurodevelopmental examination (the Kyoto Scale of Psychological Development [KSPD]) results at 18 months corrected age were available. Then, the effect of IVB on the developmental quotient (DQ) in each KSPD domain (Postural-Movement, Cognitive-Adaptive, or Language-Social domain) or the overall DQ was investigated by performing linear regression analysis. RESULTS: Out of the 513 patients reviewed, 53 were included in the study. IVB and LPC were performed for 14 and 39 patients, respectively. Administration of IVB was significantly associated with neurodevelopmental delay in the Language-Social domain (p = 0.01). The observed association remained even after adjusting for gestational age and birth weight (p = 0.03). CONCLUSIONS: Administration of IVB may introduce a risk of developmental impairment of interpersonal relationships, socializations, and/or verbal abilities of preterm children. We recommended that preterm infants who received IVB undergo a neurodevelopmental reassessment during their school years or in adulthood.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Deficiências do Desenvolvimento/etiologia , Retinopatia da Prematuridade/patologia , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Injeções Intravítreas , Japão , Transtornos do Desenvolvimento da Linguagem/etiologia , Fotocoagulação a Laser , Análise Multivariada , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
Sci Rep ; 10(1): 1851, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024929

RESUMO

Inadequate pre-pregnancy BMI and gestational weight gain (GWG) have been associated with sub-optimal child development. We used data from the 2015 Pelotas (Brazil) Birth Cohort Study. Maternal anthropometry was extracted from antenatal/hospital records. BMI (kg/m2) and GWG (kg) adequacy were classified according to WHO and IOM, respectively. Development was evaluated using the INTER-NDA assessment tool for 3,776 children aged 24 months. Suspected developmental delay (SDD) was defined as <10th percentile. Associations between maternal exposures and child development were tested using linear and logistic regressions. Mediation for the association between BMI and child development through GWG was tested using G-formula. Sex differences were observed for all child development domains, except motor. Maternal pre-pregnancy underweight increased the odds of SDD in language (OR: 2.75; 95%CI: 1.30-5.80), motor (OR: 2.28; 95%CI: 1.20-4.33), and global (OR: 2.14; 95% CI: 1.05-4.33) domains for girls; among boys, excessive GWG was associated with SDD in language (OR: 1.59; 95%CI: 1.13-2.24) and cognition (OR: 1.59; 95%CI: 1.15-2.22). Total GWG suppressed the association of pre-pregnancy BMI with percentiles of global development in the entire sample. Maternal underweight and excessive GWG were negatively associated with development of girls and boys, respectively. The association of pre-pregnancy BMI with global child development was not mediated by GWG, irrespective of child's sex.


Assuntos
Desenvolvimento Infantil/fisiologia , Deficiências do Desenvolvimento/etiologia , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Estado Nutricional/fisiologia , Adulto , Antropometria/métodos , Índice de Massa Corporal , Brasil , Criança , Estudos de Coortes , Feminino , Ganho de Peso na Gestação/fisiologia , Humanos , Modelos Logísticos , Masculino , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Gravidez , Complicações na Gravidez , Magreza/fisiopatologia , Ganho de Peso/fisiologia , Adulto Jovem
17.
Zhonghua Er Ke Za Zhi ; 58(2): 118-122, 2020 Feb 02.
Artigo em Chinês | MEDLINE | ID: mdl-32102148

RESUMO

Objective: To summarize the clinical phenotypes of epilepsy in patients with GABRA1 gene variants. Methods: A total of 11 epileptic patients (4 boys and 7 girls) who were treated in the Department of Pediatrics, Peking University First Hospital from March 2016 to July 2019 and detected with GABRA1 gene heterozygous pathogenic variants by targeted next-generation sequencing were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively. Results: A total of 11 epileptic patients carried GABRA1 gene pathogenic variants, of whom 10 were de novo variants and the other one was inherited from the patient's mother. Two patients had the same variants. Six variants were novel. Ages at seizure onset ranged from 3 to 14 months, and the median age was 8 months. The seizure was first observed within 1 year in 10 patients and beyond 1 year of age in 1 patient. Multiple seizure types were observed, including focal seizures in 10 patients, generalized tonic clonic seizures (GTCS) in 3 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. There were 5 patients with multiple seizure types. Sensitivity to fever was observed in 9 patients, among whom 6 patients had a history of status epilepticus. Two patients had photoparoxysmal response. Five patients had abnormal EEG background, and 6 patients had abnormal discharges in EEG during interictal phase. Brain magnetic resonance imaging (MRI) was normal in all patients. Developmental delay in various degrees was present in 9 patients. Among the 11 patients, Dravet syndrome was diagnosed in 5 patients, West syndrome in 2 patients, undiagnosed early-onset epileptic encephalopathy in 1 patient, and focal epilepsy in the other 3 patients. The ages at the last follow-up ranged from 8 months to 12 years. During follow-up, 8 patients were seizure-free for 6 months to 8 years, and 1 patient had discontinuation of medication. Conclusions: In epilepsy associated with GABRA1 gene variants, de novo pathogenic variants are more common than inherited. Most epilepsy caused by GABRA1 gene variants occurs in infancy. Most patients have multiple seizures and focal seizures are common. Most patients have a comparatively favorable prognosis, but they may still have varied degrees of developmental delay.


Assuntos
Encéfalo/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Epilepsia/diagnóstico , Epilepsia/genética , Convulsões/etiologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Feminino , Humanos , Lactente , Masculino , Neuroimagem , Fenótipo , Receptores de GABA-A , Estudos Retrospectivos , Espasmos Infantis/diagnóstico
18.
Am J Hum Genet ; 106(2): 256-263, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32004446

RESUMO

We report an inborn error of metabolism caused by TKFC deficiency in two unrelated families. Rapid trio genome sequencing in family 1 and exome sequencing in family 2 excluded known genetic etiologies, and further variant analysis identified rare homozygous variants in TKFC. TKFC encodes a bifunctional enzyme involved in fructose metabolism through its glyceraldehyde kinase activity and in the generation of riboflavin cyclic 4',5'-phosphate (cyclic FMN) through an FMN lyase domain. The TKFC homozygous variants reported here are located within the FMN lyase domain. Functional assays in yeast support the deleterious effect of these variants on protein function. Shared phenotypes between affected individuals with TKFC deficiency include cataracts and developmental delay, associated with cerebellar hypoplasia in one case. Further complications observed in two affected individuals included liver dysfunction and microcytic anemia, while one had fatal cardiomyopathy with lactic acidosis following a febrile illness. We postulate that deficiency of TKFC causes disruption of endogenous fructose metabolism leading to generation of by-products that can cause cataract. In line with this, an affected individual had mildly elevated urinary galactitol, which has been linked to cataract development in the galactosemias. Further, in light of a previously reported role of TKFC in regulating innate antiviral immunity through suppression of MDA5, we speculate that deficiency of TKFC leads to impaired innate immunity in response to viral illness, which may explain the fatal illness observed in the most severely affected individual.


Assuntos
Catarata/etiologia , Cerebelo/anormalidades , Deficiências do Desenvolvimento/etiologia , Mutação , Malformações do Sistema Nervoso/etiologia , Fósforo-Oxigênio Liases/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Alelos , Sequência de Aminoácidos , Catarata/patologia , Cerebelo/patologia , Pré-Escolar , Deficiências do Desenvolvimento/patologia , Feminino , Homozigoto , Humanos , Lactente , Masculino , Malformações do Sistema Nervoso/patologia , Linhagem , Fenótipo , Fosforilação , Homologia de Sequência , Sequenciamento Completo do Exoma
20.
Brain Dev ; 42(3): 298-301, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31899079

RESUMO

Mucolipidosis type IV (MLIV) is a rare lysosomal storage disorder causing severe psychomotor developmental delay and progressive visual impairment. MLIV is an autosomal recessive disease caused by mutations in MCOLN1, which encodes for mucolipin-1. Here, we report a case of a 4-year-old Japanese girl with severe intellectual disability and motor deficits. Brain magnetic resonance imaging showed signal abnormalities in the white matter and thinning of the corpus callosum. Whole-exome sequencing was performed on the proband and her parents, and novel compound heterozygous mutations at c.936_938del (p.Phe313del) and c.1503dupC (p.Ile502Hisfs*106) in MCOLN1 (NM_020533.2) were identified in the proband. Additional biochemical examinations revealed elevated serum gastrin level and iron deficiency anemia, leading to the diagnosis of MLIV. More reports of such pathogenic mutations are expected to broaden the understanding of the channel function of mucolipin-1 and genotype-phenotype correlations.


Assuntos
Corpo Caloso/patologia , Deficiências do Desenvolvimento/genética , Mucolipidoses/genética , Canais de Receptores Transientes de Potencial/genética , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Japão , Mucolipidoses/complicações
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