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1.
Eur J Med Genet ; 61(5): 280-283, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29307791

RESUMO

22q11.2 microduplication (22q11.2DupS) is associated with a broad spectrum of phenotypes, including normality. Psychiatric disorders are described in 13% of these patients, including Attention Deficit and Hyperactivity Disorder (ADHD), Intellectual Deficiency (ID), and Autism Spectrum Disorder (ASD), but not schizophrenia. We report changes in the psychiatric symptom profile in the course of development of a young boy with a 22q11.2DupS syndrome, from early childhood to adolescence. The boy's psychiatric presentation was characterized by features of Pervasive Developmental Disorder (PDD), with ADHD in early childhood, a single psychotic episode in mid-infancy, and executive impairment in adolescence. We discuss the importance of an in-depth assessment of cognitive functions in children with22q11.2DupS throughout their development.


Assuntos
Anormalidades Múltiplas/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Síndrome de DiGeorge/diagnóstico , Transtornos Psicóticos/diagnóstico , Anormalidades Múltiplas/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Transtornos Globais do Desenvolvimento Infantil/genética , Duplicação Cromossômica/genética , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Função Executiva , Humanos , Masculino , Linhagem , Transtornos Psicóticos/genética
2.
Turk Psikiyatri Derg ; 28(2): 89-94, 2017.
Artigo em Turco | MEDLINE | ID: mdl-29192941

RESUMO

OBJECTIVE: Methylphenidate is the first-choice medication for the Pervasive Developmental Disorders (PDDs), and comorbid Attention Deficit Hyperactivity Disorder (ADHD). But this approach generally results with poor outcomes, and increased adverse effects. It is aimed to investigate the comparison of cases who diagnosed with PDDs and Mild Mental Retardation (MR) and cases with pure ADHD in terms of the clinical response to MPH. Also we aimed to investigate the relations between CES-1 polymorphism gene and the clinical response to MPH. METHODS: For clarifying this we searched for three polymorphisms (Arg199/His, Ser75/Asn, and Ile49/Val) in carboxylesterase-1 gene (CES-1) in the saliva of patients diagnosed with PDD+ADHD. Also, we assessed the clinical response to MPH by dimensional approach using the Attention Deficit Hyperactivity Disorder Rating Scale IV and Clinical Global Impression-Improvement scale. RESULTS: PDD+ADHD groups had significantly higher Arg199/His polymorphism, and clinically responded poorer with symptoms sometimes even worsening to the MPH treatment compared with "pure" ADHD and ADHD+MR groups. CONCLUSION: This is the first study that an association between Arg199/His polymorphism in CES1 and altered treatment response to MPH in patients with PDD that presents with symptoms of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Hidrolases de Éster Carboxílico/genética , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Globais do Desenvolvimento Infantil/tratamento farmacológico , Metilfenidato/uso terapêutico , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estimulantes do Sistema Nervoso Central/administração & dosagem , Criança , Transtornos Globais do Desenvolvimento Infantil/genética , Pré-Escolar , Feminino , Humanos , Masculino , Metilfenidato/administração & dosagem , Variantes Farmacogenômicos , Polimorfismo Genético , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
3.
Neurología (Barc., Ed. impr.) ; 32(9): 568-578, nov.-dic. 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-169036

RESUMO

Introducción: El retraso global del desarrollo (RGD) y la discapacidad intelectual (DI) son un motivo de consulta frecuente en la consulta de Neuropediatría. Actualmente, la hibridación genómica comparada constituye una de las principales técnicas aplicadas al diagnóstico de esta patología. Resulta útil determinar qué características fenotípicas se asocian a obtener un resultado etiológico en el test genético. Métodos: Se llevó a cabo un estudio ciego pormenorizado de las características clínicas, antropométricas y morfológicas de 80 individuos afectos de DI no explicada y se analizó cuales estaban asociadas a obtener un resultado etiológico en el array-CGH. Resultados: El resultado del array fue patológico en un 27,5% de los casos. Los factores que se asociaron estadísticamente a tener una prueba de array-CGH patológica fueron los antecedentes familiares de DI/RGD (OR: 12,1), la presencia de malformaciones congénitas (OR: 5,33), más de 3 rasgos dismórficos faciales (OR: 20,9) y la hipotonía periférica (OR: 3,25). Conclusiones: Nuestros hallazgos coinciden con otras series publicadas. Por lo tanto, asumimos que la probabilidad de encontrar variación en el número de copias de significado patológico mediante array-CGH aumenta si alguna de las características anteriores está presentes en individuos afectos de DI/RGD (AU)


Introduction: Global developmental delay (GDD) and intellectual disability (ID) are frequent reasons for consultation in paediatric neurology departments. Nowadays, array comparative genomic hybridisation (array-CGH) is one of the most widely used techniques for diagnosing these disorders. Our purpose was to determine the phenotypic features associated with pathological results in this genetic test. Methods: We conducted a blind study of the epidemiological, clinical, anthropometric, and morphological features of 80 patients with unexplained ID to determine which features were associated with pathological results in array-CGH. Results: Pathological results were found in 27.5% of the patients. Factors associated with pathological results in array-CGH were a family history of GDD/ID (OR = 12.1), congenital malformations (OR = 5.33), having more than 3 facial dysmorphic features (OR = 20.9), and hypotonia (OR = 3.25). Conclusions: Our findings are consistent with those reported by other published series. We therefore conclude that the probability of having pathological results in array-CGH increases with the presence of any of the features mentioned above in patients with ID/GDD (AU)


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Deficiência Intelectual/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Hibridização Genômica Comparativa/métodos , Fenótipo , Marcadores Genéticos/genética , Facies
4.
Behav Brain Res ; 331: 92-101, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28499914

RESUMO

Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental disorders with typical triad of symptoms: impaired social interaction, language and communication abnormalities and stereotypical behavior. Despite extensive research, the etiology and pathogenesis of ASD remain largely unclear. The lack of solid knowledge on the mechanisms of these disorders decreases the opportunities for pathogenetic treatment of autism. Various theories where proposed in order to explain the pathophysiology underlying ASD. Despite the fact that none of them is able to completely explain the impairments in the nervous system of ASD patients, these hypotheses were instrumental in highlighting the most important mechanisms in the development of this complex disorder. Some new theories are based on neurovisualization studies, others on the data from genomic studies, which become increasingly available worldwide. As the research in this field is largely dependent on the animal models, there is an ongoing discussion and search for the most appropriate one adequately reproducing the pathology. Here we provide an overview of current theories of the origin and development of ASD discussed in the context of existing and proposed rodent models of ASD.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Transtorno Autístico/fisiopatologia , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Modelos Animais de Doenças , Rede Nervosa/fisiopatologia , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Comportamento/fisiologia , Transtornos Globais do Desenvolvimento Infantil/genética , Transtornos Globais do Desenvolvimento Infantil/patologia , Humanos
5.
Nat Rev Neurosci ; 18(3): 147-157, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28179641

RESUMO

Several large-scale genomic studies have supported an association between cases of autism spectrum disorder and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3, which encode a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS. An evaluation of human genetic data, as well as of in vitro and in vivo animal model data, may allow us to understand how disruption of SHANK scaffolding proteins affects the structure and function of neural circuits and alters behaviour.


Assuntos
Transtorno do Espectro Autista/metabolismo , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Neurônios/metabolismo , Sinapses/metabolismo , Animais , Transtorno do Espectro Autista/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Humanos , Mutação/genética , Proteínas do Tecido Nervoso/metabolismo
6.
Proc Natl Acad Sci U S A ; 113(52): 15054-15059, 2016 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-27956632

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.


Assuntos
Transtorno do Espectro Autista/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Deleção de Genes , Genes Essenciais , Mutação , Alelos , Animais , Encéfalo/metabolismo , Éxons , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , Camundongos , Camundongos Knockout , Fenótipo , Risco , Irmãos , Comportamento Social
7.
PLoS Genet ; 12(11): e1006425, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27846226

RESUMO

Sexual dimorphism in common disease is pervasive, including a dramatic male preponderance in autism spectrum disorders (ASDs). Potential genetic explanations include a liability threshold model requiring increased polymorphism risk in females, sex-limited X-chromosome contribution, gene-environment interaction driven by differences in hormonal milieu, risk influenced by genes sex-differentially expressed in early brain development, or contribution from general mechanisms of sexual dimorphism shared with secondary sex characteristics. Utilizing a large single nucleotide polymorphism (SNP) dataset, we identify distinct sex-specific genome-wide significant loci. We investigate genetic hypotheses and find no evidence for increased genetic risk load in females, but evidence for sex heterogeneity on the X chromosome, and contribution of sex-heterogeneous SNPs for anthropometric traits to ASD risk. Thus, our results support pleiotropy between secondary sex characteristic determination and ASDs, providing a biological basis for sex differences in ASDs and implicating non brain-limited mechanisms.


Assuntos
Transtorno do Espectro Autista/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Cromossomos Humanos X/genética , Transtorno do Espectro Autista/patologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Transtornos Globais do Desenvolvimento Infantil/patologia , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Caracteres Sexuais
9.
Psychiatr Pol ; 50(3): 543-54, 2016.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-27556113

RESUMO

Autism spectrum disorders (ASD) are caused by disruptions in early stages of central nervous system development and are usually diagnosed in first years of life. Despite common features such as impairment of socio-communicative development and stereotypical behaviours, ASD are characterised by heterogeneous course and clinical picture. The most important aetiological factors comprise genetic and environmental influences acting at prenatal, perinatal and neonatal period. The role of rare variants with large effect i.e. copy number variants in genes regulating synapse formation and intrasynaptic connections is emphasised. Common variants with small effect may also be involved, i.e. polymorphisms in genes encoding prosocial peptides system - oxytocin and vasopressin. The environmental factors may include harmful effects acting during pregnancy and labour, however their specificity until now is not confirmed, and in some of them a primary genetic origin cannot be excluded. In several instances, especially with comorbid disorders - intellectual disability, epilepsy and dysmorphias - a detailed molecular diagnostics is warranted, which currently may elucidate the genetic background of disorder in about 20% of cases.


Assuntos
Asfixia Neonatal/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Asfixia Neonatal/genética , Transtorno do Espectro Autista/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Comorbidade , Feminino , Humanos , Masculino , Gravidez , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/genética
10.
JAMA Psychiatry ; 73(6): 622-9, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27145529

RESUMO

IMPORTANCE: Previous research has focused on examining the familial clustering of schizophrenia, bipolar disorder, and autism spectrum disorders (ASD). Little is known about the clustering of other psychiatric and neurodevelopmental disorders among siblings of persons with ASD. OBJECTIVE: To examine the risk for psychiatric and neurodevelopmental disorders among full siblings of probands with ASD. DESIGN, SETTING, AND PARTICIPANTS: The Finnish Prenatal Study of Autism and Autism Spectrum Disorders used a population-based cohort that included children born from January 1, 1987, to December 31, 2005, who received a diagnosis of ASD by December 31, 2007. Each case was individually matched to 4 control participants by sex and date and place of birth. The siblings of the cases and controls were born from January 1, 1977, to December 31, 2005, and received a diagnosis from January 1, 1987, to December 31, 2009. This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers. Data were analyzed from March 6, 2014, to February 12, 2016. MAIN OUTCOMES AND MEASURES: The adjusted risk ratio (RR) for psychiatric and neurodevelopmental disorders among siblings of probands with ASD vs siblings of matched controls. Additional analyses were conducted separately for ASD subgroups, including childhood autism, Asperger syndrome, and pervasive developmental disorders not otherwise specified. Analyses were further stratified by sex and intellectual disability among the probands. RESULTS: Among the 3578 cases with ASD (2841 boys [79.4%]) and 11 775 controls (9345 boys [79.4%]), 1319 cases (36.9%) and 2052 controls (17.4%) had at least 1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (adjusted RR, 2.5; 95% CI, 2.3-2.6). The largest associations were observed for childhood-onset disorders (1061 cases [29.7%] vs 1362 controls [11.6%]; adjusted RR, 3.0; 95% CI, 2.8-3.3), including ASD (374 cases [10.5%] vs 125 controls [1.1%]; adjusted RR, 11.8; 95% CI, 9.4-14.7), tic disorders (28 cases [0.8%] vs 24 controls [0.2%]; adjusted RR, 4.3; 95% CI, 2.3-8.2), attention-deficit/hyperactivity disorder (189 cases [5.3%] vs 180 controls [1.5%]; adjusted RR, 3.7; 95% CI, 2.9-4.7), learning and coordination disorders (563 cases [15.7%] vs 697 controls [5.9%]; adjusted RR, 3.2; 95% CI, 2.8-3.6), intellectual disability (104 cases [2.9%] vs 137 controls [1.2%]; adjusted RR, 3.1; 95% CI, 2.3-4.2), conduct and oppositional disorders (180 cases [5.0%] vs 221 controls [1.9%]; adjusted RR, 2.8; 95% CI, 2.2-3.5), and emotional disorders with onset specific to childhood (126 cases [3.5%] vs 157 controls [1.3%]; adjusted RR, 2.6; 95% CI, 1.9-3.4). Autism spectrum disorders were also associated with schizophrenia spectrum disorders, affective disorders, anxiety disorders, and other neurotic and personality disorders among siblings. CONCLUSIONS AND RELEVANCE: Psychiatric and neurodevelopmental disorders cluster among siblings of probands with ASD. For etiologic research, these findings provide further evidence that several psychiatric and neurodevelopmental disorders have common risk factors.


Assuntos
Transtorno do Espectro Autista/genética , Predisposição Genética para Doença/genética , Transtornos Mentais/genética , Transtornos do Neurodesenvolvimento/genética , Irmãos , Adolescente , Análise de Variância , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/genética , Síndrome de Asperger/psicologia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Estudos de Casos e Controles , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/genética , Transtornos Globais do Desenvolvimento Infantil/psicologia , Estudos de Coortes , Comorbidade , Feminino , Finlândia , Seguimentos , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/psicologia , Risco , Irmãos/psicologia , Adulto Jovem
11.
Nat Med ; 22(4): 345-61, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27050589

RESUMO

Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies.


Assuntos
Transtorno do Espectro Autista/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Predisposição Genética para Doença , Terapia de Alvo Molecular , Animais , Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/terapia , Transtornos Globais do Desenvolvimento Infantil/patologia , Transtornos Globais do Desenvolvimento Infantil/terapia , Modelos Animais de Doenças , Humanos
12.
J Am Acad Child Adolesc Psychiatry ; 55(2): 106-13.e4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26802777

RESUMO

OBJECTIVE: Recent studies have highlighted the impact of coexisting mental health problems in autism spectrum disorders (ASD). No twin studies to date have reported on individuals meeting diagnostic criteria of ASD. This twin study reports on the etiological overlap between the diagnosis of ASD and emotional symptoms, hyperactivity, and conduct problems measured with the Strengths and Difficulties Questionnaire. METHOD: Genetic and environmental influences on the covariance between ASD and coexisting problems were estimated, in line with the correlated risks model prediction. Phenotypic causality models were also fitted to explore alternative explanations of comorbidity: namely, that coexisting problems are the result of or result in ASD symptoms; that they increase recognition of ASD; or that they arise due to an over-observation bias/confusion when differentiating between phenotypes. RESULTS: More than 50% of twins with broad spectrum/ASD met the borderline/abnormal levels cut-off criteria for emotional symptoms or hyperactivity, and approximately 25% met these criteria for the 3 reported problems. In comparison, between 13% and 16% of unaffected twins scored above the cut-offs. The phenotypic correlation between ASD and emotional symptoms was explained entirely by genetic influences and accompanied by a moderate genetic correlation (0.42). The opposite was true for the overlap with conduct problems, as nonshared-environmental factors had the strongest impact. For hyperactivity, the best-fitting model suggested a unidirectional phenotypic influence of hyperactivity on ASD. CONCLUSION: Our findings suggest a possible effect of hyperactivity on identification of ASD. The lack of genetic influences on conduct problems-ASD overlap further supports the genetic independence of these 2 phenotypes. Finally, the co-occurrence of emotional symptoms in ASD, compared to other co-occurring problems, is completely explained by common genetic effects.


Assuntos
Transtorno do Espectro Autista/etiologia , Agitação Psicomotora/etiologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Espectro Autista/psicologia , Criança , Transtornos Globais do Desenvolvimento Infantil/etiologia , Transtornos Globais do Desenvolvimento Infantil/genética , Comorbidade , Emoções , Feminino , Genética Comportamental , Humanos , Masculino , Saúde Mental , Fenótipo , Agitação Psicomotora/genética , Agitação Psicomotora/psicologia , Gêmeos/genética , Gêmeos/psicologia
13.
Pediatr. aten. prim ; 17(68): 309-315, oct.-dic. 2015. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-146928

RESUMO

Introducción: se realiza una revisión del número de trastornos del neurodesarrollo en la población pediátrica de un centro de Atención Primaria de la ciudad de Zaragoza (España), con el objetivo de conocer la prevalencia y la importancia creciente del diagnóstico genético. Material y métodos: se realiza una búsqueda de casos en el programa de historia clínica informatizada OMI6 con los siguientes términos: 'retraso mental', 'retraso del desarrollo', 'trastorno del desarrollo', 'autismo'. Resultados: se han obtenido 76 casos de trastornos del neurodesarrollo, que son el 2,19% de la población. Los diagnósticos principales fueron: 23 trastornos del lenguaje, 17 trastornos del aprendizaje, 11 de retraso mental, 10 casos de trastorno del espectro autista (TEA), 8 de retraso del desarrollo, 5 casos de dislexia, un caso de síndrome de Asperger y un caso de dispraxia motora. Se solicitó estudio genético en 21 casos, el 27,63% de los niños, siendo mucho más frecuente su realización en casos de retraso mental o TEA. Las pruebas genéticas proporcionaron el diagnóstico en 12 pacientes de los estudiados, un 57,14% de los casos. En general, se encuentra una causa genética en el 75% de los casos con diagnóstico establecido. Conclusiones: este estudio muestra que los trastornos del neurodesarrollo aparecen en nuestra población con una frecuencia similar a la descrita en la bibliografía médica. Los estudios genéticos permiten cada vez más un diagnóstico etiológico preciso (AU)


Introduction: we review the number of neurodevelopmental disorders in the pediatric population of a primary care center in Zaragoza, in order to determine the prevalence and the growing importance of genetic diagnosis. Material and methods: the research was carried out in the computerized medical record programme OMI6 with the following terms: 'mental retardation', 'development delay', 'development disorders' and 'autism spectrum disorders'. Results: 76 cases of neurodevelopment disorders have been got, which mean 2.19% of the population of study. The main diagnoses were: 23 language disorders, 17 learning disorders, 11 mental retardation, 10 cases of autism, 8 development delay, 5 cases of dyslexia, 1 case of Asperger´s syndrome and 1 case of dyspraxia. A genetic study was requested in 21 cases, which supposed the 27.63% of children, being more frequent implementation in cases of mental retardation or autism. Genetic test provided diagnosis in 12 patients of the study, which means the 57.14% of the cases. A genetic cause was found in the 75% of the cases with an established diagnosis. Conclusion: this study shows that neurodevelopmental disorders appear in our population with a similar frequency described in the literature. Genetic studies increasingly allow precise etiological diagnosis (AU)


Assuntos
Humanos , Retardo Mental Ligado ao Cromossomo X/epidemiologia , Deficiência Intelectual/genética , Técnicas Genéticas , Transtorno Autístico/genética , Transtornos Globais do Desenvolvimento Infantil/genética
14.
Undersea Hyperb Med ; 42(4): 353-9, 2015 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26403019

RESUMO

PURPOSE: To determine whether hyperbaric oxygen (HBO2) therapy should be used for the treatment of autism spectrum disorders (ASD). METHODS: A literature search was performed on PubMed, Cochrane Library and DynaMed for studies evaluating the use of HBO2 for ASD treatment. The studies were then reviewed for the highest quality evidence. RESULTS: The evidence is weak for the use of HBO2 in ASD, with only one, likely flawed, randomized control study showing treatment benefit. CONCLUSIONS: HBO2 should not be recommended for ASD treatment until more conclusive favorable results and long-term outcomes are demonstrated from well-designed controlled trials.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/terapia , Oxigenação Hiperbárica/métodos , Transtorno Autístico/fisiopatologia , Transtorno Autístico/terapia , Circulação Cerebrovascular , Criança , Transtornos Globais do Desenvolvimento Infantil/genética , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Encefalite/terapia , Humanos
15.
Yi Chuan ; 37(9): 845-54, 2015 09.
Artigo em Inglês | MEDLINE | ID: mdl-26399524

RESUMO

Autism spectrum disorders (ASDs) are common neurodevelopmental disorders characterized by impaired social communication, restricted and repetitive behavior or interests. Over the past 40 years, the reported prevalence for ASDs has been steadily rising world-wide. Due to the application of large-scale exome sequencing in recent years, hundreds of novel ASD associated genes have been identified. These associated genes are enriched in several common genetic signaling pathways such as synapse formation and chromatin remodeling. Intensive studies in animal models have revealed abnormal synaptic plasticity and an imbalanced ratio of excitatory to inhibitory neurotransmission in neural circuits of ASD brains. In this review, we summarize recent advances in (1) genetic heterogeneity of ASDs, (2) molecular pathways disturbed by various genetic mutations in ASDs, and (3) the development of genetic diagnostics and pharmacological treatments for ASDs. This review aims to provide a brief overview of the genetic basis of ASDs and prospects for diagnosis and treatment for ASDs.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Animais , Transtornos Globais do Desenvolvimento Infantil/tratamento farmacológico , Montagem e Desmontagem da Cromatina , Variações do Número de Cópias de DNA , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Mutação , Plasticidade Neuronal
17.
JAMA ; 314(9): 895-903, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26325558

RESUMO

IMPORTANCE: The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. OBJECTIVE: To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. DESIGN, SETTING, AND PARTICIPANTS: The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). EXPOSURES: All probands underwent CMA, with WES performed for 95 proband-parent trios. MAIN OUTCOMES AND MEASURES: The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. RESULTS: Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. CONCLUSIONS AND RELEVANCE: Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Exoma , Análise em Microsséries/métodos , Técnicas de Diagnóstico Molecular/métodos , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/genética , Transtorno Autístico/diagnóstico , Transtorno Autístico/genética , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/patologia , Pré-Escolar , Feminino , Humanos , Masculino , Análise em Microsséries/estatística & dados numéricos , Técnicas de Diagnóstico Molecular/estatística & dados numéricos , Mutação , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Fenótipo , Análise de Sequência de DNA/métodos , Análise de Sequência de Proteína/métodos
19.
Pharmacol Res ; 102: 71-80, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26408203

RESUMO

The etiology of autism spectrum disorders (ASDs) still remains unclear and seems to involve a considerable overlap between polygenic, epigenetic and environmental factors. We have summarized the current understanding of the interplay between gene expression dysregulation via epigenetic modifications and the potential epigenetic impact of environmental factors in neurodevelopmental deficits. Furthermore, we discuss the scientific controversies of the relationship between prenatal exposure to alcohol and alcohol-induced epigenetic dysregulations, and gene expression alterations which are associated with disrupted neural plasticity and causal pathways for ASDs. The review of the literature suggests that a better understanding of developmental epigenetics should contribute to furthering our comprehension of the etiology and pathogenesis of ASDs and fetal alcohol spectrum disorders.


Assuntos
Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/genética , Epigênese Genética/genética , Etanol/efeitos adversos , Transtornos do Espectro Alcoólico Fetal/etiologia , Transtornos do Espectro Alcoólico Fetal/genética , Animais , Transtornos Globais do Desenvolvimento Infantil/etiologia , Transtornos Globais do Desenvolvimento Infantil/genética , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética
20.
Zh Vyssh Nerv Deiat Im I P Pavlova ; 65(3): 259-70, 2015 May-Jun.
Artigo em Russo | MEDLINE | ID: mdl-26281226

RESUMO

The purpose of this article is to provide the overview of visual cognitive development in subjects with FMRP deficit. Description of fragile X mental retardation syndrome is presented in the article, that is the most common cause of inherited intellectual disability and one of the most prevalent genetic causes of autism spectrum disorder. The syndrome is associated with deficit of fragile X mental retardation protein following FMR1-gene mutation. Researches of static and dynamic object perception, face perception and oculomotor control are discussed in the article. The results obtained by subjects with FX syndrome are compared with ASD data, syndrome with closed behavioral phenotype. Several factors that underlie visual cognitive deficit are discussed in the article.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Cognição , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Transtornos Globais do Desenvolvimento Infantil/genética , Transtornos Globais do Desenvolvimento Infantil/psicologia , Feminino , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/psicologia , Expressão Gênica , Humanos , Masculino , Percepção de Movimento , Mutação , Reconhecimento Visual de Modelos
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