Etiological Investigation of Autism Spectrum Disorders – State of The Art

Authors

  • Daniel Gonçalves Unit of Neurodevelopment, Department of Pediatrics, Hospital Pediátrico Integrado, Centro Hospitalar de São João
  • Micaela Guardiano Unit of Neurodevelopment, Department of Pediatrics, Hospital Pediátrico Integrado, Centro Hospitalar de São João
  • Miguel Leão Unit of Neurogenetics, Department of Medical Genetics, Centro Hospitalar de São João

DOI:

https://doi.org/10.25753/BirthGrowthMJ.v27.i3.12106

Keywords:

Autism, genetics, neurodevelopment

Abstract

Autism Spectrum Disorder is a Neurodevelopmental Disorder characterized by deficits in social interaction and by the presence of restricted, repetitive and stereotyped patterns of behaviours, interests, and activities. The aetiology of Autism Spectrum Disorder is often genetic, with several monogenic diseases clearly associated with this disorder. Significant advances in molecular genetics have increased the rate of etiological diagnosis of Autism Spectrum Disorder to about 30-40% in the last decade.
The establishment of a definitive etiological diagnosis facilitates referral to community support services, contributes to knowledge of possible associated medical conditions and prevention of morbidity and mortality, while also eliminating inadequate diagnostic tests and allowing individualized genetic counselling.
The authors present a proposal for an etiological investigation of this pathology, including criteria for performing complementary metabolic evaluation, neuroimaging and electroencephalography, and various genetic studies (conventional cytogenetics, Array-Comparative Genomic Hybridization, targeted molecular studies, multi-gene panels and Whole Exome Sequencing).

References

Autism spectrum disorder. In: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, American Psychiatric Association, Arlington, VA 2013. p.50.

Blaxill MF. What's going on? The question of time trends in autism.

Public Health Rep. 2004; 119(6):536-51 (ISSN: 0033-3549)

Rutter M. Incidence of autism spectrum disorders: changes over time and their meaning.

Acta Paediatr. 2005 Jan;94(1):2-15.

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010

Surveillance Summaries. March 28, 2014 / 63(SS02);1-21

Oliveira GG. Epidemiologia do autismo em Portugal : um estudo de prevalência da perturbação do espectro do autismo e de caracterização de uma amostra populacional de idade escolar (Tese de Doutoramento).

Universidade de Coimbra, Portugal. 2005

Schaefer GB1, Mendelsohn NJ; Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions.

Genet Med. 2013 May;15(5):399-407. doi: 10.1038/gim.2013.32. Epub 2013 Mar 21.

Geschwind DH. Genetics of autism spectrum disorders.

Trends Cogn Sci (Regul Ed) 2011;15:409–416.

Miles JH. Autism spectrum disorders – a genetics review.

Genet Med 2011; 13: 278–94.

Zecavati N, Spence SJ. Neurometabolic disorders and dysfunction in autism spectrum disorders.

Curr Neurol Neurosci Rep 2009;9:129–136.

Boddaert N, Zilbovicius M, Philipe A, et al. MRI findings in 77 children with non-syndromic autistic disorder.

PLoS ONE 2009;4:e4415

Boutros NN, Renee Lajiness-O’Neill, Andrew Zillgitt, Anette E Richard, Susan M Bowyer. ,EEG changes associated with autistic spectrum disorders

Neuropsychiatric Electrophysiology 2015; 1:3

Tuchman R. CSWS-related autistic regression versus autistic regression without CSWS.

Epilepsia, 50 (Suppl. 7):18-20, 2009

El-Fishawy P, State MW. The genetics of autism: key issues, recent findings, and clinical implications.

Psychiatr Clin North Am 2010;33:83–105

Tammimies K et al. Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.

JAMA. 2015;314(9):895-903. doi:10.1001/jama.2015.10078

Jeste SS, Geschwind DH. Disentangling the hetero-geneity of autism spectrum disorder through genetic findings.

Nat Rev Neurol 10:74-81

Vorstman JA, Staal WG, van Daalen E, van Engeland H, Hochstenbach PF, Franke L. Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism.

Mol Psychiatry 2006;11:1,18–28

Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.

Am J Hum Genet 2010;86:749–764

Pinkel D,, Albertson DG (2005) Array comparative genomic hybridization and its applications in cancer.

Nat Genet 37:11-17.

Schaefer GB, Starr L, Pickering D, Skar G, Dehaai K, Sanger WG. Array

comparative genomic hybridization findings in a cohort referred for an autism evaluation.

J Child Neurol 2010;25:1498–1503

Clifford S, Dissanayake C, Bui QM, Huggins R, Taylor AK, Loesch DZ. Autism spectrum phenotype in males and females with fragile X full mutation and premutation.

J Autism Dev Disord 2007;37:738–747

Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

Nat Genet. 1999;23(2):185.

Hammer S, Dorrani N, Dragich J, Kudo S, Schanen C. The phenotypic

consequences of MECP2 mutations extend beyond Rett syndrome.

Ment Retard Dev Disabil Res Rev 2002;8:94–98.

Beyer KS, Blasi F, Bacchelli E, Klauck SM, Maestrini E, Poustka A; International Molecular Genetic Study of Autism Consortium (IMGSAC). Mutation analysis of the coding sequence of the MECP2 gene in infantile autism.

Hum Genet 2002;111:305–309

Zappella M, Meloni I, Longo I, et al. Study of MECP2 gene in Rett syndrome variants and autistic girls.

Am J Med Genet B Neuropsychiatr Genet 2003;119B:102–107

Stanich P, Lindor NM. PTEN Hamartoma tumor syndrome, including Cowden Syndrome.

UpToDate Aug 23, 2016.

Butler MG, Dasouki MJ, Zhou XP, Talebizadeh Z, Brown M, Takahashi TN, Miles JH, Wang CH, Stratton R, Pilarski R, Eng C. Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.

J Med Genet. 2005 Apr;42(4):318-21.

Varga EA, Pastore M, Prior T, Herman GE, McBride KL. The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.

Genet Med 2009;11:111–117.

Bock I, et al. Targeted next generation sequencing of a panel of autism-related genes identifies an EHMT1 mutation in a Kleefstra syndrome patient with autism and normal intellectual performance.

Gene 2016

Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting.

Brain Res 2011;1380:42–77.

Yaping Yang et. al. Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders

N Engl J Med 2013; 369:1502-1511October 17, 2013

Sener EF, Canatan H, Ozkul Y. Recent Advances in Autism Spectrum Disorders: Applications of Whole Exome Sequencing Technology.

Psychiatry Investig. 2016 May;13(3):255-64. doi: 10.4306/pi.2016.13.3.255. Epub 2016 May 18.

Yuen RK et al. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.

Nature Neuroscience. 2017. Epub ahead of print. Office is

Downloads

Published

2018-10-17

How to Cite

Gonçalves, D., Guardiano, M., & Leão, M. (2018). Etiological Investigation of Autism Spectrum Disorders – State of The Art. NASCER E CRESCER - BIRTH AND GROWTH MEDICAL JOURNAL, 27(3), 176–181. https://doi.org/10.25753/BirthGrowthMJ.v27.i3.12106

Issue

Section

Review Articles