Possibilities of early diagnosis of autism spectrum disorder, with a special attention to Asperger syndrome: A systematic literature review
More details
Hide details
Department of Family Medicine and Infectious Diseases, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Poland
Submission date: 2020-08-19
Final revision date: 2020-11-16
Acceptance date: 2020-11-17
Online publication date: 2020-12-14
Publication date: 2020-12-14
Corresponding author
Beata Januszko-Giergielewicz   

Department of Family Medicine and Infectious Diseases, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-082 Olsztyn, Poland.
Pol. Ann. Med. 2021;28(1):99-105
On May 18, 2013, the American Psychiatric Association introduced new diagnostic criteria, the so-called DSM-5, in which Asperger syndrome, autism, childhood disintegrative disorder, also known as Heller’s syndrome, and pervasive developmental disorders were classified as autism spectrum disorder (ASD). Based on the DSM-5 classification, Asperger syndrome can be described more specifically as ASD with specifiers, such as, for example, ‘without intellectual impairment’ and ‘without structural language impairment.’ The new classification assumes that typical symptoms, such as inflexible, stereotypical behavioral patterns do not necessarily have to appear in early childhood. The new standardizations limited falsely positive diagnoses; unfortunately, at the same time, reducing the specificity of diagnosis.

The aim of this work, based on a systematic literature review, is to discuss various diagnostic procedures conducive to timely diagnosis of ASD.

Material and methods:
The source data were identified based on predefined primary medical headings: ASD, Asperger syndrome, and autism and the following keywords: diagnostic, epidemiology, genetic, prenatal, postnatal, DSM-5, and DSM-IV. The following databases were searched: PubMed, Google Scholar (searching using work titles) and UpToDate.

Results and discussion:
Proper anamnesis, good medical and parental care, and the application of adequate diagnostic procedures might be conducive to a much earlier diagnosis, approximately at the age of 2. Owing to parental perceptive observation as well as genetic and imaging examinations a group of children at a higher risk might be precisely identified, consequently facilitating a quicker diagnosis.

Early diagnosis contributes to improved developmental outcomes.

None declared.
None declared.
Yu KK, Cheung C, Chua SE, McAlonan GM. Can Asperger syndrome be distinguished from autism? An anatomic likelihood meta-analysis of MRI studies. J Psychiatry Neurosci. 2011;36(6):412–421.
Darcy-Mahoney A, Minter B, Higgins M, Guo Y, Zauche LH, Hirst J. Maternal and neonatal birth factors affecting the age of ASD diagnosis. Newborn Infant Nurs Rev. 2016;16(4):340–347.
Bonnet-Brilhault F. L’autisme: un trouble neuro-développemental précoce. Arch Pédiatrie. 2017;24(4):384–390.
Baxter AJ, Brugha T, Erskine HE, Scheurer RW, Vos T, Scott JG. The epidemiology and global burden of autism spectrum disorders. Psychol Medicine. 2015;45(3):601–613.
Kogan MD, Vladutiu CJ, Schieve LA, et al. The prevalence of parent-reported autism spectrum disorder among US children. Pediatrics. 2018;142(6):e20174161.
Piskorz-Ogórek K, Ogórek S, Cieślińska A, Kostyra E. Autism in Poland in comparison to other countries. Pol Ann Med. 2015;22(1):35–40.
Weiss EM, Gschaidbauer B, Kaufmann L, et al. Age-related differences in inhibitory control and memory updating in boys with Asperger syndrome. Eur Arch Psychiatry Clin Neurosci. 2017;267(7):651–659.
Cooper R. Understanding the DSM-5: stasis and change. Hist Psychiatry. 2018;29(1):49–65.
Wiggins LD, Rice CE, Barger B, et al. DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool children. Soc Psychiatry Psychiatr Epidemiol. 2019;54(6):693–701.
Dell’Osso L, Dalle Luche R, Gesi C, Moroni I, Carmassi C, Maj M. From Asperger’s autistischen psychopathen to DSM-5 autism spectrum disorder and beyond: a subthreshold autism spectrum model. Clin Pract Epidemiol Ment Health. 2016;12:120–131.
McPartland JC, Reichow B, Volkmar FR. Sensitivity and specificity of proposed DSM-5 diagnostic criteria for autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012;51(4):368–383.
Abuse S. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, MD: Substance Abuse and Mental Health Services Administration. 2016. Accessed: 18.08.2020.
Regier DA, Kuhl EA, Kupfer DJ. The DSM‐5: Classification and criteria changes. World Psychiatry. 2013;12(2):92–98.
Vahia VN. Diagnostic and statistical manual of mental disorders 5: A quick glance. Indian J Psychiatry. 2013;55(3):220–223. http://www.indianjpsychiatry.o... 55/3/220/117131.
WHO. The ICD-10 classification of mental and behavioural disorders. Diagnostic criteria for research. Geneva: World Health Organization; 1993. Accessed: 18.08.2020.
Maenner MJ, Rice CE, Arneson CL, et al. Potential impact of DSM-5 criteria on autism spectrum disorder prevalence estimates. JAMA Psychiatry. 2014;71(3):292–300.
Smith O, Jones SC. ‘Coming Out’with Autism: Identity in People with an Asperger’s Diagnosis After DSM-5. J Autism Dev Disord. 2020;50(2):592–602.
Arksey H, O’Malley L. Scoping studies: Towards a methodological framework. IJSRM. 2005;8(1):19–32.
Williams JG, Higgins JP, Brayne CE. Systematic review of prevalence studies of autism spectrum disorders. Arch Dis Child. 2006;91(1):8–15.
Isaksson J, Tammimies K, Neufeld J, et al. EU-AIMS Longitudinal European Autism Project (LEAP): the autism twin cohort. Mol Autism. 2018;9(1):26.
Parner ET, Thorsen P, Dixon G, et al. A comparison of autism prevalence trends in Denmark and Western Australia. J Autism Dev Disord. 2011;41(12):1601–1608.
Simashkova N, Ivanov M, Kozlovskaya G, Makushkin E. Total screening of the risk of developing mental illness of young children in primary health care in Russia (data 2017). Eur Psychiatry. 2019;56(S1):54.
Duchan E, Patel DR. Epidemiology of autism spectrum disorders. Pediatr Clin. 2012;59(1):27–43.
Perera H, Wijewardena K, Aluthwelage R. Screening of 18–24-month-old children for autism in a semi-urban community in Sri Lanka. J Trop Pediatr. 2009;55(6):402–405.
Al-Mendalawi M. Prevalence of autism spectrum disorders among children (1–10 years of age): findings of a midterm report from Northwest India. J Postgrad Med. 2016;62(1):52–53.
Hunter DJ, Reddy KS. Noncommunicable diseases. N Engl J Med. 2013;369(14):1336–1343.
Kim JY, Son MJ, Son CY, et al. Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence. Lancet Psychiatry. 2019;6(7):590–600.
Hansen SN, Schendel DE, Francis RW, et al. Recurrence risk of autism in Siblings and Cousins: A multinational, population-based study. J Am Acad Child Adolesc Psychiatry. 2019;58(9):866–875.
Chambers NJ, Wetherby AM, Stronach ST, Njongwe N, Kauchali S, Grinker RR. Early detection of autism spectrum disorder in young isiZulu-speaking children in South Africa. Autism. 2017;21(5):518–526.
Jokiranta-Olkoniemi E, Cheslack-Postava K, Joelsson P, Suominen A, Brown AS, Sourander A. Attention-deficit/hyperactivity disorder and risk for psychiatric and neurodevelopmental disorders in siblings. Psychol Med. 2019;49(1):84–91.
Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA. 2014;311(17):1770–1777.
Bailey A, Le Couteur A, Gottesman I, et al. Autism as a strongly genetic disorder: Evidence from a British twin study. Psychol Med. 1995;25(1):63–77.
Devlin B, Scherer SW. Genetic architecture in autism spectrum disorder. Curr Opin Genet Dev. 2012;22(3):229–237.
ARNT2 Single Gene. Accessed: 12.07.2020.
Hirose K, Morita M, Ema M, et al. cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor (Arnt2) with close sequence similarity to the aryl hydrocarbon receptor nuclear translocator (Arnt). Mol Cell Biol. 1996;16(4):1706–1713.
Webb E, AlMutair A Kelberman D, et al. ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies. Brain. 2013;136(10):3096–3105.
Aitola MH, Pelto-Huikko MT. Expression of Arnt and Arnt2 mRNA in developing murine tissues. J Histochem Cytochem. 2003;51(1):41–54.
Karthik L, Kumar G, Keswani T, Bhattacharyya A, Chandar SS, Rao KB. Protease inhibitors from marine actinobacteria as a potential source for antimalarial compound. PloS One. 2014;9(3):e90972.
Di Napoli A, Warrier V, Baron-Cohen S, Chakrabarti B. Genetic variant rs17225178 in the ARNT2 gene is associated with Asperger Syndrome. Mol Autism. 2015;6(1):9.
Durdiaková J, Warrier V, Baron-Cohen S, Chakrabarti B. Single nucleotide polymorphism rs6716901 in SLC25A12 gene is associated with Asperger syndrome. Mol Autism. 2014;5(1):1–5.
Wibom R, Lasorsa FM, Töhönen V, et al. AGC1 deficiency associated with global cerebral hypomyelination. N Eng J Med. 2009;361(5):489–495.
SLC25A12. Accessed: 12.07.2020.
Gilby KL, O’Brien TJ. Epilepsy, autism, and neurodevelopment: kindling a shared vulnerability? Epilepsy Behav. 2013;26(3):370–374.
Sharma P, Powell KL, Wlodek ME, O’Brien TJ, Gilby KL. Delayed myelination and neurodevelopment in male seizure‐prone versus seizure‐resistant rats. Epilepsia. 2018;59(4):753–764.
Park JT, Shahid AM, Jammoul A. Common pediatric epilepsy syndromes. Pediatr Ann. 2015;44(2):e30–e35.
Rolls ET. The cingulate cortex and limbic systems for emotion, action, and memory. Brain Struct Funct. 2019;224:3001–3018.
Oblak AL, Gibbs TT, Blatt GJ. Decreased GABAB receptors in the cingulate cortex and fusiform gyrus in autism. J Neurochem. 2010;114(5):1414–1423.
Frye RE, Casanova MF, Fatemi SH, et al. Neuropathological mechanisms of seizures in autism spectrum disorder. Front Neurosci. 2016;10:192.
Guptill JT, Booker AB, Gibbs TT, Kemper TL, Bauman ML, Blatt GJ. [3H]-Flunitrazepam-labeled benzodiazepine binding sites in the hippocampal formation in autism: A multiple concentration autoradiographic study. J Autism Dev Disord. 2007;37(5):911–920.
Oblak A, Gibbs T, Blatt G. Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism. Autism Res. 2009;2(4):205–219.
Xu G, Strathearn L, Liu B, et al. Prevalence and treatment patterns of autism spectrum disorder in the United States, 2016. JAMA Pediatr. 2019;173(2):153–159.
Bonnet‐Brilhault F, Rajerison TA, Paillet C, et al. Autism is a prenatal disorder: Evidence from late gestation brain overgrowth. Autism Res. 2018;11(12):1635–1642.
Johnson CP, Myers SM; American Academy of Pediatrics Council on Children With Disabilities. Identification and evaluation of children with autism spectrum disorder. Pediatrics. 2007;120(5):1183–1215.
Ellerbeck K, Smith C, Courtemanche A. Care of children with autism spectrum disorder. Prim Care. 2015;42(1):85–98.
Whitehouse AJ, Hickey M, Stanley FJ, Newnham JP, Pennell CE. Brief report: A preliminary study of fetal head circumference growth in autism spectrum disorder. J Autism Dev Disord. 2011;41(1):122–129.
Weiss LA, Shen Y, Korn JM, et al. Association between microdeletion and microduplication at 16p11. 2 and autism. N Eng J Med. 2008;358(7):667–675.
Rynkiewicz A. [Autism spectrum disorder in girls. Sex differences in clinical manifestation and co-occuring psychopathology] [master’s thesis]. Gdańsk: Gdański Uniwersytet Medyczny; 2016 [in Polish].
Grigg-Damberger MM. The visual scoring of sleep in infants 0 to 2 months of age. J Clin Sleep Med. 2016;12(3):429–445.
Korotchikova I, Stevenson NJ, Livingstone V, Ryan CA, Boylan GB. Sleep–wake cycle of the healthy term newborn infant in the immediate postnatal period. Clin Neurophysiol. 2016;127(4):2095–2101.
Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL. Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2017;56(11):948–957. e4.
Nummenmaa L, Engell AD, Von Dem Hagen E, Henson RN, Calder AJ. Autism spectrum traits predict the neural response to eye gaze in typical individuals. Neuroimage. 2012;59(4):3356–3363.
Hodges H, Fealko C, Soares N. Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation. Transl Pediatr. 2020;9(Suppl 1):S55–S65.
Domes G, Kumbier E, Heinrichs M, Herpertz SC. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology. 2014;39(3):698–706.
Klin A, Jones W, Schultz R, Volkmar F, Cohen D. Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism. Arch Gen Psych. 2002;59(9):809–816.
Campbell DB, Datta D, Jones ST, et al. Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder. J Neurodev Disord. 2011;3(2):101–112.
Bakermans-Kranenburg MJ, Van Ijzendoorn MH. A sociability gene? Meta-analysis of oxytocin receptor genotype effects in humans. Psychiatr Genet. 2014;24(2):45–51.
Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005;435(7042):673–676.
Murphy CM, Deeley Q, Daly E, et al. Anatomy and aging of the amygdala and hippocampus in autism spectrum disorder: an in vivo magnetic resonance imaging study of Asperger syndrome. Autism Res. 2012;5(1):3–12.
Mosconi MW, Cody-Hazlett H, Poe MD, Gerig G, Gimpel-Smith R, Piven J. Longitudinal study of amygdala volume and joint attention in 2-to 4-year-old children with autism. Arch Gen Psychiatry. 2009;66(5):509–516.
Donovan AP, Basson MA. The neuroanatomy of autism – a developmental perspective. J Anat. 2017;230(1):4–15.
Goji A, Ito H, Mori K, et al. Assessment of anterior cingulate cortex (ACC) and left cerebellar metabolism in Asperger’s syndrome with proton magnetic resonance spectroscopy (MRS). PLoS One. 2017;12(1):e0169288.
Robins DL, Casagrande K, Barton M, Chen C-MA, Dumont-Mathieu T, Fein D. Validation of the modified checklist for autism in toddlers, revised with follow-up (M-CHAT-R/F). Pediatrics. 2014;133(1):37–45.
Nygren G, Sandberg E, Gillstedt F, Ekeroth G, Arvidsson T, Gillberg C. A new screening programme for autism in a general population of Swedish toddlers. Res Dev Disabil. 2012;33(4):1200–1210.
Weissman L. Autism spectrum disorder: Screening tools. Accessed: 12.07.2020.
Journals System - logo
Scroll to top