Transtorno do Espectro do Autismo: uma revisão sobre etiologia, epigenética e mutação de novo
Palavras-chave:
Transtorno Autístico; Mutação; Metilação; Revisão.Resumo
A pessoa com o Transtorno do Espectro do Autismo (TEA) compartilha sintomas centrais no comprometimento de três áreas do neurodesenvolvimento: deficits de habilidades sociais, deficits de habilidades comunicativas e presença de comportamentos, interesses e/ou atividades restritos, repetitivos e estereotipados. O aumento na prevalência desse transtorno é preocupante e reforça a necessidade de se investigar os seus principais fatores de risco. Assim, o presente estudo teve como finalidade apresentar uma revisão da literatura a respeito do TEA, sua etiologia, aspectos epigenéticos e mutação de novo. Para o mapeamento deste estudo tomou-se como base bibliográfica a Base de Dados Pubmed. Os resultados apontam que o TEA é caracterizando como um transtorno de herança multifatorial e que fatores ambientais, independentes ou em conjunto com os fatores genéticos, aumentam o risco desse transtorno. Além disso, estudos moleculares têm destacado o papel das mutações de novo e da epigenética no desenvolvimento do TEA.
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Referências
BRASIL. Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Ações Programáticas Estratégicas. Diretrizes de Atenção à Reabilitação da Pessoa com Transtornos do Espectro do Autismo (TEA). Brasília: Ministério da Saúde, 2014: [online] 88. Disponível em:
AMERICAN PSYCHIATRIC ASSOCIATION. Manual diagnóstico e estatístico de transtornos mentais: DSM-III- R. São Paulo: Manole; 1989.
AMERICAN PSYCHIATRIC ASSOCIATION. Manual diagnóstico e estatístico de transtornos mentais: DSM-IV. São Paulo: Manole; 1994.
AMERICAN PSYCHIATRIC ASSOCIATION. Manual diagnóstico e estatístico de transtornos mentais: DSM-V. Porto Alegre: Artmed; 2014. p. 50-59.
WORLD HEALTH ORGANIZATION. The ICD-10 Classification of Mental and Behavioural Disorders. Geneva; 1992.
Junior WC. Custo familiar com autismo infantil. Belo Horizonte: Instituto de Previdência dos Servidores do Estado de Minas Gerais; 2010.
Voineagu I, Eapen V. Converging Pathways in Autism Spectrum Disorders: Interplay between Synaptic Dysfunction and Immune Responses. Frontiers in human neuroscience. 2013;7:738.
Aldinger KA, Lane CJ, Veenstra-Vander WJ, Levitt P. Patterns of Risk for Multiple Co-Occurring Medical Conditions Replicate Across Distinct Cohorts of Children with Autism Spectrum Disorder. Autism research: official journal of the International Society for Autism Research. 2015;8(6):771-81.
Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism research : official journal of the International Society for Autism Research. 2012;5(2):101-8.
Loke YJ, Hannan AJ, Craig JM. The Role of Epigenetic Change in Autism Spectrum Disorders. Frontiers in neurology 2015;6:107.
Zerbo O, Leong A, Barcellos L, Bernal P, Fireman B, Croen LA. Immune mediated conditions in autism spectrum disorders. Brain, behavior, and immunity. 2015;46:232-6.
Fombonne E. Epidemiology of pervasive developmental disorders. Pediatric research 2009;65:591-8.
CENTERS FOR DISEASE CONTROL AND PREVENTION. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010. Atlanta, GA: MMWR Surveill Summ; 2014. p1-21.
CENTERS FOR DISEASE CONTROL AND PREVENTION. Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring network, United States, 2006. Atlanta, GA: MMWR Surveill Summ; 2009. p. 1–20.
CENTERS FOR DISEASE CONTROL AND PREVENTION. Prevalence of autism spectrum disorders - autism and developmental disabilities monitoring network, 14 sites, United States, 2002. Washington D.C: MMWR Surveill Summ; 2007. p. 12-28.
Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, et al. Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study. Pediatrics. 2011.
Feinberg JI, Bakulski KM, Jaffe AE, Tryggvadottir R, Brown SC, Goldman LR, et al. Paternal sperm DNA methylation associated with early signs of autism risk in na autism-enriched cohort. International journal of epidemiology. 2015;44(4):1199-210.
Lejarraga H, Menendez AM, Menzano E, Guerra L, Biancato S, Pianelli P, et al. Screening for developmental problems at primary care level: a field programme in San Isidro, Argentina. Paediatric and perinatal epidemiology. 2008;22(2):180-7.
Montiel-Nava C, Pena JA. Epidemiological findings of pervasive developmental disorders in a Venezuelan study. Autism : the international journal of research and practice. 2008;12(2):191-202.
Van Balkom ID, Bresnahan M, Vogtlander MF, van Hoeken D, Minderaa RB, Susser E, et al. Prevalence of treated autism spectrum disorders in Aruba. Journal of neurodevelopmental disorders. 2009;1(3):197-204.
Paula CS, Ribeiro SH, Fombonne E, Mercadante MT. Brief report: prevalence of pervasive developmental disorder in Brazil: a pilot study. Journal of autism and developmental disorders. 2011;41(12):1738-42.
Grether JK, Rosen NJ, Smith KS, Croen LA. Investigation of shifts in autismo reporting in the California Department of Developmental Services. Journal of autism and developmental disorders. 2009;39(10):1412-9.
Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology. 2009;20(1):84-90.
Crafa D, Warfa N. Maternal migration and autism risk: systematic analysis. International review of psychiatry. 2015;27(1):64-71.
Lavelle TA, Weinstein MC, Newhouse JP, Munir K, Kuhlthau KA, Prosser LA. Economic Burden of Childhood Autism Spectrum Disorders. Pediatrics. 2014.
Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?. Environmental epigenetics. 2016;2.
Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Archives of general psychiatry 2011;68:1095-102.
LaSalle JM. Epigenomic strategies at the interface of genetic and environmental risk factors for autism. Journal of human genetics. 2013;58(7):396-401.
Nardone S, Elliott E. The Interaction between the Immune System and Epigenetics in the Etiology of Autism Spectrum Disorders. Frontiers in neuroscience. 2016;10:329.
Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012;485:237-41.
Tordjman S, Somogyi E, Coulon N, et al. Gene x Environment interactions in autismo spectrum disorders: role of epigenetic mechanisms. Frontiers in psychiatry 2014;5:53.
Bailey A, Le Couteur A, Gottesman I, et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychological medicine 1995;25:63-77.
Nordenbaek C, Jorgensen M, Kyvik KO, Bilenberg N. A Danish population-based twin study on autism spectrum disorders. European child & adolescent psychiatry 2014;23:35-43.
Colvert E, Tick B, McEwen F, Stewart C, Curran SR, Woodhouse E, et al. Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample. JAMA psychiatry. 2015;72(5):415-23.
Byars SG, Boomsma JJ. Opposite differential risks for autism and schizophrenia based on maternal age, paternal age, and parental age differences. Evolution, medicine, and public health 2016;286-98.
Geier DA, Kern JK, Sykes LK, Geier MR. Examining genotypic variation in autismo spectrum disorder and its relationship to parental age and phenotype. The application of clinical genetics 2016;9:121-9.
Tsang SY, Ahmad T, Mat FW, Zhao C, Xiao S, Xia K, Xue H. Variation of global DNA methylation levels with age and in autistic children. Hum Genomics. 2016;10(1):31.
Kong A, Frigge ML, Masson G, et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature 2012;488:471-5.
Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reproductive biology and endocrinology : RB&E 2015;13:35.
Wong WS, Solomon BD, Bodian DL, et al. New observations on maternal age effect on germline de novo mutations. Nature communications 2016;7:10486.
Parner ET, Baron-Cohen S, Lauritsen MB, et al. Parental age and autism spectrum disorders. Annals of epidemiology 2012;22:143-50.
Sandin S, Hultman CM, Kolevzon A, Gross R, MacCabe JH, Reichenberg A. Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry 2012;51:477-86.
Flanagan JM, Popendikyte V, Pozdniakovaite N, Sobolev M, Assadzadeh A, Schumacher A, et al. Intra- and interindividual epigenetic variation in human germ cells. American journal of human genetics. 2006;79(1):67-84.
Ge ZJ, Schatten H, Zhang CL, Sun QY. Oocyte ageing and epigenetics. Reproduction 2015;149:R103-14.
Liu L, Van Groen T, Kadish I, Li Y, Wang D, James SR, et al. Insufficient DNA methylation affects healthy aging and promotes age-related health problems. Clin Epigenetics. 2011;2(2):349-60.
Reik W, Dean W. DNA methylation and mammalian epigenetics. Electrophoresis, 2001;22:2838-2843.
Markunas CA, Wilcox AJ, Xu Z, Joubert BR, Harlid S, Panduri V, et al. Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults. PloS one 2016;11(7).
AMERICAN PSYCHIATRIC ASSOCIATION. Manual diagnóstico e estatístico de transtornos mentais: DSM-III- R. São Paulo: Manole; 1989.
AMERICAN PSYCHIATRIC ASSOCIATION. Manual diagnóstico e estatístico de transtornos mentais: DSM-IV. São Paulo: Manole; 1994.
AMERICAN PSYCHIATRIC ASSOCIATION. Manual diagnóstico e estatístico de transtornos mentais: DSM-V. Porto Alegre: Artmed; 2014. p. 50-59.
WORLD HEALTH ORGANIZATION. The ICD-10 Classification of Mental and Behavioural Disorders. Geneva; 1992.
Junior WC. Custo familiar com autismo infantil. Belo Horizonte: Instituto de Previdência dos Servidores do Estado de Minas Gerais; 2010.
Voineagu I, Eapen V. Converging Pathways in Autism Spectrum Disorders: Interplay between Synaptic Dysfunction and Immune Responses. Frontiers in human neuroscience. 2013;7:738.
Aldinger KA, Lane CJ, Veenstra-Vander WJ, Levitt P. Patterns of Risk for Multiple Co-Occurring Medical Conditions Replicate Across Distinct Cohorts of Children with Autism Spectrum Disorder. Autism research: official journal of the International Society for Autism Research. 2015;8(6):771-81.
Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism research : official journal of the International Society for Autism Research. 2012;5(2):101-8.
Loke YJ, Hannan AJ, Craig JM. The Role of Epigenetic Change in Autism Spectrum Disorders. Frontiers in neurology 2015;6:107.
Zerbo O, Leong A, Barcellos L, Bernal P, Fireman B, Croen LA. Immune mediated conditions in autism spectrum disorders. Brain, behavior, and immunity. 2015;46:232-6.
Fombonne E. Epidemiology of pervasive developmental disorders. Pediatric research 2009;65:591-8.
CENTERS FOR DISEASE CONTROL AND PREVENTION. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010. Atlanta, GA: MMWR Surveill Summ; 2014. p1-21.
CENTERS FOR DISEASE CONTROL AND PREVENTION. Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring network, United States, 2006. Atlanta, GA: MMWR Surveill Summ; 2009. p. 1–20.
CENTERS FOR DISEASE CONTROL AND PREVENTION. Prevalence of autism spectrum disorders - autism and developmental disabilities monitoring network, 14 sites, United States, 2002. Washington D.C: MMWR Surveill Summ; 2007. p. 12-28.
Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, et al. Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study. Pediatrics. 2011.
Feinberg JI, Bakulski KM, Jaffe AE, Tryggvadottir R, Brown SC, Goldman LR, et al. Paternal sperm DNA methylation associated with early signs of autism risk in na autism-enriched cohort. International journal of epidemiology. 2015;44(4):1199-210.
Lejarraga H, Menendez AM, Menzano E, Guerra L, Biancato S, Pianelli P, et al. Screening for developmental problems at primary care level: a field programme in San Isidro, Argentina. Paediatric and perinatal epidemiology. 2008;22(2):180-7.
Montiel-Nava C, Pena JA. Epidemiological findings of pervasive developmental disorders in a Venezuelan study. Autism : the international journal of research and practice. 2008;12(2):191-202.
Van Balkom ID, Bresnahan M, Vogtlander MF, van Hoeken D, Minderaa RB, Susser E, et al. Prevalence of treated autism spectrum disorders in Aruba. Journal of neurodevelopmental disorders. 2009;1(3):197-204.
Paula CS, Ribeiro SH, Fombonne E, Mercadante MT. Brief report: prevalence of pervasive developmental disorder in Brazil: a pilot study. Journal of autism and developmental disorders. 2011;41(12):1738-42.
Grether JK, Rosen NJ, Smith KS, Croen LA. Investigation of shifts in autismo reporting in the California Department of Developmental Services. Journal of autism and developmental disorders. 2009;39(10):1412-9.
Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology. 2009;20(1):84-90.
Crafa D, Warfa N. Maternal migration and autism risk: systematic analysis. International review of psychiatry. 2015;27(1):64-71.
Lavelle TA, Weinstein MC, Newhouse JP, Munir K, Kuhlthau KA, Prosser LA. Economic Burden of Childhood Autism Spectrum Disorders. Pediatrics. 2014.
Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?. Environmental epigenetics. 2016;2.
Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Archives of general psychiatry 2011;68:1095-102.
LaSalle JM. Epigenomic strategies at the interface of genetic and environmental risk factors for autism. Journal of human genetics. 2013;58(7):396-401.
Nardone S, Elliott E. The Interaction between the Immune System and Epigenetics in the Etiology of Autism Spectrum Disorders. Frontiers in neuroscience. 2016;10:329.
Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012;485:237-41.
Tordjman S, Somogyi E, Coulon N, et al. Gene x Environment interactions in autismo spectrum disorders: role of epigenetic mechanisms. Frontiers in psychiatry 2014;5:53.
Bailey A, Le Couteur A, Gottesman I, et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychological medicine 1995;25:63-77.
Nordenbaek C, Jorgensen M, Kyvik KO, Bilenberg N. A Danish population-based twin study on autism spectrum disorders. European child & adolescent psychiatry 2014;23:35-43.
Colvert E, Tick B, McEwen F, Stewart C, Curran SR, Woodhouse E, et al. Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample. JAMA psychiatry. 2015;72(5):415-23.
Byars SG, Boomsma JJ. Opposite differential risks for autism and schizophrenia based on maternal age, paternal age, and parental age differences. Evolution, medicine, and public health 2016;286-98.
Geier DA, Kern JK, Sykes LK, Geier MR. Examining genotypic variation in autismo spectrum disorder and its relationship to parental age and phenotype. The application of clinical genetics 2016;9:121-9.
Tsang SY, Ahmad T, Mat FW, Zhao C, Xiao S, Xia K, Xue H. Variation of global DNA methylation levels with age and in autistic children. Hum Genomics. 2016;10(1):31.
Kong A, Frigge ML, Masson G, et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature 2012;488:471-5.
Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reproductive biology and endocrinology : RB&E 2015;13:35.
Wong WS, Solomon BD, Bodian DL, et al. New observations on maternal age effect on germline de novo mutations. Nature communications 2016;7:10486.
Parner ET, Baron-Cohen S, Lauritsen MB, et al. Parental age and autism spectrum disorders. Annals of epidemiology 2012;22:143-50.
Sandin S, Hultman CM, Kolevzon A, Gross R, MacCabe JH, Reichenberg A. Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry 2012;51:477-86.
Flanagan JM, Popendikyte V, Pozdniakovaite N, Sobolev M, Assadzadeh A, Schumacher A, et al. Intra- and interindividual epigenetic variation in human germ cells. American journal of human genetics. 2006;79(1):67-84.
Ge ZJ, Schatten H, Zhang CL, Sun QY. Oocyte ageing and epigenetics. Reproduction 2015;149:R103-14.
Liu L, Van Groen T, Kadish I, Li Y, Wang D, James SR, et al. Insufficient DNA methylation affects healthy aging and promotes age-related health problems. Clin Epigenetics. 2011;2(2):349-60.
Reik W, Dean W. DNA methylation and mammalian epigenetics. Electrophoresis, 2001;22:2838-2843.
Markunas CA, Wilcox AJ, Xu Z, Joubert BR, Harlid S, Panduri V, et al. Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults. PloS one 2016;11(7).
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Publicado
05-03-2020
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Alves Maia, F. ., Tereza Carvalho Almeida, M., Bruno da Silva, V. ., Rachel Alves, M. ., & Fagundes Silveira, M. (2020). Transtorno do Espectro do Autismo: uma revisão sobre etiologia, epigenética e mutação de novo. Revista Renome, 6(1), 101–114. Recuperado de https://www.periodicos.unimontes.br/index.php/renome/article/view/1243
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