CoChat
Sign Up
Cited by 31Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersWilliams Syndrome Research

Profiles of autism characteristics in thirteen genetic syndromes: a machine learning approach

Open access
Bozhilova, Natali, Welham, Alice, Adams, Dawn, Bissell, Stacey, Bruining, Hilgo, Crawford, Hayley, Eden, Kate, Nelson, Lisa +9 more·2023·Molecular Autism
DOI 10.1186/s13229-022-00530-5PMC PMC9837969
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of > 1500 individuals with rare genetic syndromes. Methods: Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n = 154, Cri du Chat n = 75, Cornelia de Lange n = 199, fragile X n = 297, Prader–Willi n = 278, Lowe n = 89, Smith–Magenis n = 54, Down n = 135, Sotos n = 40, Rubinstein–Taybi n = 102, 1p36 deletion n = 41, tuberous sclerosis complex n = 83 and Phelan–McDermid n = 35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n = 254). Self-help skills were included as an additional predictor. Results: Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader–Willi, Rubinstein–Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith–Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy. Limitations: The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups. Conclusions: These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s13229-022-00530-5

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Syndromic ASD is associated with identifiable genetic or genomic syndromes, often accompanied by intellectual disability as well as somatic or neurological abnormalities.

    “In contrast, syndromic ASD is associated with identifiable genetic or genomic syndromes, often accompanied by ID as well as somatic or neurological abnormalities (Bozhilova et al., 2023).”

    From Biological hierarchy from genotype to phenotype in syndromic and non-syndromic autism spectrum disorder (2026) · cites this paper as Bozhilova et al., 2023

    The Background (page unavailable) links autistic characteristics in known genetic syndromes with intellectual disability, and the Methods > Participants section compares people with genetic syndromes against autistic people without a known genetic syndrome. The paper does not establish the claim that syndromic ASD is often accompanied by somatic or neurological abnormalities. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 43

  1. [1]Tick B Bolton P Happé F Rutter M Rijsdijk F Heritability of autism spectrum disorders: a meta-analysis of twin studies J Child Psychol Psychiatry 2016 57 5 585 595 10.1111/jcpp.12499 26709141 PMC4996332 · DOI · Paper page
  2. [2]Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013. 24413388
  3. [4]Havdahl A Niarchou M Starnawska A Uddin M van der Merwe C Warrier V Genetic contributions to autism spectrum disorder Psychol Med. 2021 51 2260 2273 10.1017/S0033291721000192 33634770 PMC8477228 · DOI
  4. [5]Ronald A Happé F Plomin R The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism Dev Sci 2005 8 5 444 458 10.1111/j.1467-7687.2005.00433.x 16048517 · DOI · Paper page
  5. [6]Ronald A Happé F Bolton P Butcher LM Price TS Wheelwright S Genetic heterogeneity between the three components of the autism spectrum: a twin study J Am Acad Child Adolesc Psychiatry 2006 45 6 691 699 10.1097/01.chi.0000215325.13058.9d 16721319 · DOI · Paper page
  6. [7]Dworzynski K Happé F Bolton P Ronald A Relationship between symptom domains in autism spectrum disorders: a population based twin study J Autism Dev Disord 2009 39 8 1197 1210 10.1007/s10803-009-0736-1 19373549 · DOI · Paper page
  7. [8]Warrier V Toro R Won H Leblond CS Cliquet F Delorme R Social and non-social autism symptoms and trait domains are genetically dissociable Commun Biol 2019 2 1 1 13 10.1038/s42003-019-0558-4 31508503 PMC6722082 · DOI · Paper page
  8. [10]Robinson EB Koenen KC McCormick MC Munir K Hallett V Happé F A multivariate twin study of autistic traits in 12-year-olds: testing the fractionable autism triad hypothesis Behav Genet 2012 42 2 245 255 10.1007/s10519-011-9500-3 21927971 PMC3256271 · DOI
  9. [11]Ronald A Larsson H Anckarsäter H Lichtenstein P A twin study of autism symptoms in Sweden Mol Psychiatry 2011 16 10 1039 1047 10.1038/mp.2010.82 20644553 · DOI · Paper page
  10. [13]Muhle R Trentacoste SV Rapin I The genetics of autism Pediatrics 2004 113 5 e472 e486 10.1542/peds.113.5.e472 15121991 · DOI · Paper page
  11. [14]Persico AM Bourgeron T Searching for ways out of the autism maze: genetic, epigenetic and environmental clues Trends Neurosci 2006 29 7 349 358 10.1016/j.tins.2006.05.010 16808981 · DOI · Paper page
  12. [15]Oliver C Berg K Moss J Arron K Burbidge C Delineation of behavioral phenotypes in genetic syndromes: characteristics of autism spectrum disorder, affect and hyperactivity J Autism Dev Disord 2011 41 8 1019 1032 10.1007/s10803-010-1125-5 21080217 · DOI
  13. [16]Richards C Jones C Groves L Moss J Oliver C Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis The Lancet Psychiatry 2015 2 10 909 916 10.1016/S2215-0366(15)00376-4 26341300 · DOI
  14. [18]Cornish K Scerif G Karmiloff-Smith A Tracing syndrome-specific trajectories of attention across the lifespan Cortex 2007 43 6 672 685 10.1016/S0010-9452(08)70497-0 17710820 · DOI · Paper page
  15. [19]Hall SS Lightbody AA Hirt M Rezvani A Reiss AL Autism in fragile X syndrome: A category mistake? J Am Acad Child Adolesc Psychiatry 2010 49 9 921 933 10.1016/j.jaac.2010.07.001 20732628 PMC2943372 · DOI
  16. [20]Mount RH Charman T Hastings RP Reilly S Cass H Features of autism in Rett syndrome and severe mental retardation J Autism Dev Disord 2003 33 4 435 442 10.1023/A:1025066913283 12959422 · DOI
  17. [21]Moss J Howlin P The assessment and presentation of autism spectrum disorders in genetic syndromes: implications for diagnosis, intervention and understanding the wider ASD population J Intellect Disabil Res 2009 53 852 872 10.1111/j.1365-2788.2009.01197.x 19708861 · DOI
  18. [22]Moss J Howlin P Magiati I Oliver C Characteristics of autism spectrum disorder in Cornelia de Lange syndrome J Child Psychol Psychiatry 2012 53 8 883 891 10.1111/j.1469-7610.2012.02540.x 22490014 · DOI
  19. [23]Trillingsgaard A Østergaard JR Autism in Angelman syndrome: an exploration of comorbidity Autism 2004 8 2 163 174 10.1177/1362361304042720 15165432 · DOI
  20. [24]Lee NR Niu X Zhang F Clasen LS Kozel BA Smith A Variegation of autism related traits across seven neurogenetic disorders Transl Psychiatry 2022 12 1 1 10 10.1038/s41398-022-01895-0 35393403 PMC8989950 · DOI
  21. [25]Chawner SJ Doherty JL Anney RJ Antshel KM Bearden CE Bernier R A genetics-first approach to dissecting the heterogeneity of autism: phenotypic comparison of autism risk copy number variants Am J Psychiatry 2021 178 1 77 86 10.1176/appi.ajp.2020.20010015 33384013 PMC8022239 · DOI · Paper page
  22. [27]Moss JF Oliver C Berg K Kaur G Jephcott L Cornish K Prevalence of autism spectrum phenomenology in Cornelia de Lange and Cri du Chat syndromes Am J Ment Retard 2008 113 4 278 291 10.1352/0895-8017(2008)113[278:POASPI]2.0.CO;2 18564888 · DOI
  23. [28]Sloneem J Moss J Powell S Hawkins C Fosi T Richardson H The prevalence and profile of autism in Sturge-Weber syndrome J Autism Dev Disord 2022 52 5 1942 1955 10.1007/s10803-021-05062-0 34043129 · DOI
  24. [29]Bruining H Eijkemans MJ Kas MJ Curran SR Vorstman JA Bolton PF Behavioral signatures related to genetic disorders in autism Mol Autism 2014 5 1 1 12 10.1186/2040-2392-5-11 24517317 PMC3936826 · DOI · Paper page
  25. [32]Kushlick A Blunden R Cox G A method of rating behaviour characteristies for use in large scale surveys of mental handicap Psychol Med 1973 3 4 466 478 10.1017/S0033291700054271 4762223 · DOI
  26. [33]Wilde L Wade K Eden K Moss J de Vries P Oliver C Persistence of self-injury, aggression and property destruction in children and adults with tuberous sclerosis complex J Intellect Disabil Res 2018 62 12 1058 1071 10.1111/jir.12472 29417652 · DOI
  27. [34]Moss J Oliver C Arron K Burbidge C Berg K The prevalence and phenomenology of repetitive behavior in genetic syndromes J Autism Dev Disord 2009 39 4 572 588 10.1007/s10803-008-0655-6 19037716 · DOI
  28. [37]Chang C-C Lin C-J LIBSVM: a library for support vector machines ACM Trans Intell Syst Technol (TIST) 2011 2 3 1 27 10.1145/1961189.1961199 · DOI · Paper page
  29. [38]Moss J Howlin P Hastings RP Beaumont S Griffith GM Petty J Social behavior and characteristics of autism spectrum disorder in Angelman, Cornelia de Lange, and Cri du Chat syndromes Am J Intellect Dev Disabil 2013 118 4 262 283 10.1352/1944-7558-118.4.262 23937369 · DOI
  30. [39]Moss J Oliver C Nelson L Richards C Hall S Delineating the profile of autism spectrum disorder characteristics in Cornelia de Lange and fragile X syndromes Am J Intellect Dev Disabil 2013 118 1 55 73 10.1352/1944-7558-118.1.55 23301903 · DOI
  31. [40]Moss J Nelson L Powis L Waite J Richards C Oliver C A comparative study of sociability in Angelman, Cornelia de Lange, Fragile X, Down and Rubinstein Taybi syndromes and autism spectrum disorder Am J Intellect Dev Disabil 2016 121 6 465 486 10.1352/1944-7558-121.6.465 27802104 · DOI
  32. [41]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 4 738 747 10.1007/s10803-006-0205-z 17031449 · DOI
  33. [42]Klusek J Martin GE Losh M A comparison of pragmatic language in boys with autism and fragile X syndrome J Speech Lang Hear Res 2014 57 5 1692 1707 10.1044/2014_JSLHR-L-13-0064 24686468 PMC4177023 · DOI
  34. [43]Smith LE Barker ET Seltzer MM Abbeduto L Greenberg JS Behavioral phenotype of fragile X syndrome in adolescence and adulthood Am J Intellect Dev Disabil 2012 117 1 1 17 10.1352/1944-7558-117.1.1 22264109 PMC3388941 · DOI
  35. [44]Harris SW Hessl D Goodlin-Jones B Ferranti J Bacalman S Barbato I Autism profiles of males with fragile X syndrome Am J Ment Retard 2008 113 6 427 438 10.1352/2008.113:427-438 19127654 PMC2629645 · DOI · Paper page
  36. [45]Capal JK Williams ME Pearson DA Kissinger R Horn PS Murray D Profile of autism spectrum disorder in tuberous sclerosis complex: results from a longitudinal, prospective, multisite study Ann Neurol 2021 90 6 874 886 10.1002/ana.26249 34668231 PMC8639652 · DOI
  37. [46]Lee M Martin GE Berry-Kravis E Losh M A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome J Neurodev Disord 2016 8 1 1 10 10.1186/s11689-016-9179-0 28050218 PMC5203725 · DOI
  38. [47]Jeste SS Varcin KJ Hellemann GS Gulsrud AC Bhatt R Kasari C Symptom profiles of autism spectrum disorder in tuberous sclerosis complex Neurology 2016 87 8 766 772 10.1212/WNL.0000000000003002 27440144 PMC4999317 · DOI
  39. [49]Zyga O Russ S Ievers-Landis CE Dimitropoulos A Assessment of pretend play in Prader–Willi syndrome: a direct comparison to autism spectrum disorder J Autism Dev Disord 2015 45 4 975 987 10.1007/s10803-014-2252-1 25241008 · DOI
  40. [51]Woodbury-Smith M Scherer SW Progress in the genetics of autism spectrum disorder Dev Med Child Neurol 2018 60 5 445 451 10.1111/dmcn.13717 29574884 · DOI
  41. [52]Bai D Yip BHK Windham GC Sourander A Francis R Yoffe R Association of genetic and environmental factors with autism in a 5-country cohort JAMA Psychiat 2019 76 10 1035 1043 10.1001/jamapsychiatry.2019.1411 PMC6646998 31314057 · DOI · Paper page
  42. [53]Karimi P Kamali E Mousavi SM Karahmadi M Environmental factors influencing the risk of autism J Res Med Sci Offi J Isfahan Univ Med Sci 2017 22 27 PMC5377970 28413424
  43. [54]Cochran L, Moss J, Nelson L, Oliver C, editors. Contrasting age related changes in autism spectrum disorder phenomenology in Cornelia de Lange, fragile X, and Cri du Chat syndromes: results from a 2.5 year follow‐up. American Journal of Medical Genetics Part C: Seminars in Medical Genetics; 2015: Wiley Online Library. 25989416

Cited by

Sorted by citations

Authors
Bozhilova, N., Welham, A., Adams, D., Bissell, S., Bruining, H., Crawford, H., Eden, K., Nelson, L., Oliver, C., Powis, L., Richards, C., Waite, J., Watson, P., Rhys, H., Wilde, L., Woodcock, K., & Moss, J.
Affiliations
  • University of Surrey (GB)
  • University of Leicester (GB)
  • Griffith University (AU)
  • University of Birmingham (GB)
  • Amsterdam University Medical Centers (NL)
  • University of Warwick (GB)
  • Aston University (GB)
  • MRC Cognition and Brain Sciences Unit (GB)
  • The Francis Crick Institute (GB)
  • The Open University (GB)
Corresponding author
Moss, Joanna
ORCID
Venue
Molecular Autism
Publisher
Springer Science and Business Media LLC
Published
2023-01-13
Volume
14
Issue
1
Pages
3-3
ISSN
2040-2392 (ISSN-L)
DOI
10.1186/s13229-022-00530-5
PMC
PMC9837969
OpenAlex
W4315866063
Cited by
31
References
7
Citations by year
2026: 1 · 2025: 12 · 2024: 8 · 2023: 10
FWCI
4.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Autism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • University of Birmingham Research Portal (University of Birmingham) (publishedVersion, cc-by)
  • Open Research Online (The Open University) (acceptedVersion, other-oa)
  • Aston Publications Explorer (Aston University) (acceptedVersion, other-oa)
  • Warwick Research Archive Portal (University of Warwick) (acceptedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Griffith Research Online (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Apollo
  • Apollo (cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • Cerebra
  • Cornelia de Lange Syndrome Foundation, UK & Ireland
  • Research Autism
  • Newlife the Charity for Disabled Children
  • Baily Thomas Charitable Fund
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
Keywords
genetic syndromes, intellectual disability, Social Communication Questionnaire, autism spectrum disorder, phenotypic profiles, Angelman syndrome, fragile X syndrome, Prader-Willi syndrome, Cornelia de Lange syndrome, Rubinstein-Taybi syndrome, tuberous sclerosis complex, Phelan-McDermid syndrome, self-help skills, support needs assessment
MeSH terms
Autistic Disorder, Cross-Sectional Studies, Humans, Intellectual Disability, Syndrome, Tuberous Sclerosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review