ABSTRACT
Autism spectrum disorder (ASD) is a neurodevelopmental disorder, with strong genetic influences as evidenced by its high heritability. Submicroscopic variations (ranging from one kilobase to several megabases) in DNA, called copy number variations (CNVs), have been associated with psychiatric diseases, including ASD. We aimed to identify CNVs in children diagnosed with idiopathic ASD. We used microarray-based comparative genomic hybridization analysis to detect the CNVs, and bioinformatic tools to evaluate their pathogenic potential, based on predicted functional aspects. Using combined cytogenetic and bioinformatic tools, we identified an autism network of genes/proteins related to the CNVs. Among the 40 children analyzed, we found 14 potentially pathogenic CNVs, including those previously associated with ASD (located at 16p11.2, 15q11.2, and 7p21 regions). We suggest that the most relevant biological process and functional attributes involve olfactory receptors. The CNV-related autism network comprised 90 proteins and 754 nodes and indicated the family of olfactory receptors as a significant pathway in ASD. Olfactory receptors were previously associated with neurologic diseases, and they are possibly related to cognition. This integrative analysis that combines cytogenetics and bioinformatics is a promising approach to understand complex conditions such as ASD.
Subject(s)
Autism Spectrum Disorder/genetics , DNA Copy Number Variations , Receptors, Odorant/genetics , Child , Female , Gene Regulatory Networks , Humans , Male , Protein Interaction Maps , Receptors, Odorant/metabolism , Signal TransductionABSTRACT
The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80% of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.
Subject(s)
Child Development Disorders, Pervasive/physiopathology , Developmental Disabilities/physiopathology , Adult , Age Factors , Child , Child Development Disorders, Pervasive/diagnosis , Developmental Disabilities/diagnosis , Disease Progression , Female , Follow-Up Studies , Humans , Male , PrognosisABSTRACT
INTRODUCTION: During the birth, physiological changes occur in virtually all organs of the child, including the central nervous system. In this transitional phase, it is possible some degree of hypoxemia, generally well tolerated by the newborn. But, if neonatal hypoxia is intense and continuous it can lead to neonatal encephalopathy, which characterizes a critical situation for the infant. The proper approach is essential to ensure a good long-term prognosis. DEVELOPMENT: We up-to-date information regarding hypoxia neonatal and review recent evidence-based medicine publications addressing its approach. CONCLUSIONS: Neonatal encephalopathy may be clinically classified into three levels of intensity. Mild cases usually have a good prognosis, moderate intensity cases have 30% chance of sequels, and severe intensity cases have more than 70% mortality and nearly all survivors have sequels. Recent advances occurred in two areas: in the diagnosis, with new EEG and MRI techniques, and in the treatment, with the advent of therapeutic hypothermia. There is the possibility of future use for stem cell therapy. The prognosis depends on the clinical classification, the neuroimaging data as well as the EEG.
TITLE: Avances en el abordaje de la hipoxia neonatal.Introduccion. Durante el nacimiento, ocurren cambios fisiologicos en practicamente todos los organos del niño, incluyendo el sistema nervioso central. En esta fase de transicion, es posible un cierto grado de hipoxemia, en general bien tolerado por el neonato. Sin embargo, si la hipoxia neonatal es muy intensa y continuada, puede instalarse una encefalopatia neonatal, lo que caracteriza una situacion critica para el recien nacido. Su abordaje adecuado es imprescindible para garantizar un buen pronostico a largo plazo. Desarrollo. Se actualizan las informaciones acerca de la hipoxia neonatal y se revisan publicaciones recientes acerca de los avances en su abordaje a traves de la medicina basada en evidencias. Conclusiones. La encefalopatia neonatal se puede clasificar desde el punto de vista clinico en tres niveles de intensidad. Usualmente, los casos leves tienen un buen pronostico, los casos de intensidad moderada tienen un 30% de posibilidad de secuelas y los de intensidad grave tienen mas del 70% de mortalidad, pero practicamente todos los supervivientes tendran secuelas. Los avances ocurrieron en dos areas: en el diagnostico, con nuevas tecnicas de EEG y RM, y en el tratamiento, con la aparicion de la hipotermia terapeutica. Existe la posibilidad de un uso futuro para la terapia con celulas madre. El pronostico depende de la clasificacion clinica, de los datos de neuroimagen y del EEG.
Subject(s)
Asphyxia Neonatorum/therapy , Acidosis/etiology , Anticonvulsants/therapeutic use , Asphyxia Neonatorum/diagnosis , Brain Damage, Chronic/etiology , Brain Damage, Chronic/pathology , Cerebral Palsy/etiology , Combined Modality Therapy , Diagnosis, Differential , Disease Management , Epilepsy/drug therapy , Epilepsy/etiology , Humans , Infant, Newborn , Prognosis , Randomized Controlled Trials as Topic , Symptom AssessmentABSTRACT
The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80
of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.
Subject(s)
Developmental Disabilities/physiopathology , Child Development Disorders, Pervasive/physiopathology , Adult , Child , Developmental Disabilities/diagnosis , Age Factors , Female , Humans , Male , Prognosis , Disease Progression , Follow-Up Studies , Child Development Disorders, Pervasive/diagnosisABSTRACT
The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80
of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.
Subject(s)
Child Development Disorders, Pervasive/physiopathology , Developmental Disabilities/physiopathology , Adult , Age Factors , Child , Child Development Disorders, Pervasive/diagnosis , Developmental Disabilities/diagnosis , Disease Progression , Female , Follow-Up Studies , Humans , Male , PrognosisABSTRACT
OBJECTIVE: To translate into Brazilian Portuguese the Autism Diagnostic Interview-Revised (ADI-R), an extremely useful diagnostic tool in autism. METHODS: A case-control study was done to validate the ADI-R. After being translated, the interview was applied in a sample of 20 patients with autism and 20 patients with intellectual disability without autism, in order to obtain the initial psychometric properties. RESULTS: The internal consistency was high, with a of Crombach of 0.967. The validity of criterion had sensitivity and specificity of 100%, having as a gold standard the DSM-IV diagnostic criteria. The interview had high discriminant validity, with higher scores in the group of patients with autism, as well as high interobserver consistency, with median kappa of 0.824. CONCLUSION: The final version of ADI-R had satisfactory psychometric characteristics, indicating good preliminary validation properties. The instrument needs to be applied in bigger samples in other areas of the country.
Subject(s)
Autistic Disorder/diagnosis , Interview, Psychological , Adolescent , Brazil , Case-Control Studies , Child , Cultural Characteristics , Female , Humans , Language , Male , Reproducibility of Results , Sensitivity and Specificity , TranslatingABSTRACT
OBJECTIVE: To translate into Brazilian Portuguese the Autism Diagnostic Interview-Revised (ADI-R), an extremely useful diagnostic tool in autism. METHODS: A case-control study was done to validate the ADI-R. After being translated, the interview was applied in a sample of 20 patients with autism and 20 patients with intellectual disability without autism, in order to obtain the initial psychometric properties. RESULTS: The internal consistency was high, with a of Crombach of 0.967. The validity of criterion had sensitivity and specificity of 100 percent, having as a gold standard the DSM-IV diagnostic criteria. The interview had high discriminant validity, with higher scores in the group of patients with autism, as well as high interobserver consistency, with median kappa of 0.824. CONCLUSION: The final version of ADI-R had satisfactory psychometric characteristics, indicating good preliminary validation properties. The instrument needs to be applied in bigger samples in other areas of the country.
OBJETIVO: Traduzir para o português do Brasil a ADI-R (Autism Diagnostic Interview-Revised), uma ferramenta diagnóstica extremamente útil em casos de autismo. MÉTODOS: Foi realizado um estudo caso-controle para validar a ADI-R. A fim de se obter as propriedades psicométricas iniciais da entrevista, após a tradução, a ADI-R foi aplicada em uma amostra de 20 pacientes com autismo e 20 controles com retardo mental sem autismo. RESULTADOS: A consistência interna foi alta, com um a de Crombach de 0,976. A validade de critério mostrou uma sensibilidade e uma especificidade de 100 por cento, tendo os critérios diagnósticos do DSM-IV como padrão ouro. A entrevista teve uma alta validade discriminante, com maiores escores no grupo de pacientes com autismo, bem como uma alta consistência entre observadores, com um Kappa médio de 0,824. CONCLUSÃO: A versão final da ADI-R teve características psicométricas satisfatórias, indicando boas propriedades preliminares de validação. O instrumento necessita ser aplicado em amostras maiores em outras áreas do país.
Subject(s)
Adolescent , Child , Female , Humans , Male , Autistic Disorder/diagnosis , Interview, Psychological , Brazil , Case-Control Studies , Cultural Characteristics , Language , Reproducibility of Results , Sensitivity and Specificity , TranslatingABSTRACT
OBJECTIVE: To validate CHIPPS (Children's and Infants' Postoperative Pain Scale) in Brazilian children. BACKGROUND: Cross-validation is needed in order to apply this scale in a different language and culture. METHODS: We applied a Portuguese version of CHIPPS to 100 children aged 0 to 5 years. The scale was translated and tested for inter-rater reliability, internal consistency, and construct, content, and concurrent validity. The children's behavior was videotaped before, during and after a procedure in a primary care unit. Three observers then rated pain behavior from videotapes. RESULTS: The scale showed excellent inter-rater reliability (intraclass correlation coefficient: 0.89) and a very good internal consistency, with Cronbach's alpha of 0.86. The positive correlation between CHIPPS and Modified Behavior Pain Scale supports concurrent (criterion) validity (Spearman coefficient 0.70 before and 0.81 after vaccinations). Construct validity was determined by comparing the scores of each child before vaccination (without pain) and during the procedure (experiencing pain), and the difference in pain scores was statistically significant (Wilcoxon signed rank test; P < 0.001). Content validity (by expert review) was very good. CONCLUSIONS: Based on the results obtained, we can infer that CHIPPS is a valid and reliable tool for Brazilian children aged 0 to 5 years old.
