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Open Access 01-12-2022 | Attention Deficit Hyperactivity Disorder | Research

Delineating the autistic phenotype in children with neurofibromatosis type 1

Authors: Anita K. Chisholm, Kristina M. Haebich, Natalie A. Pride, Karin S. Walsh, Francesca Lami, Alex Ure, Tiba Maloof, Amanda Brignell, Melissa Rouel, Yael Granader, Alice Maier, Belinda Barton, Hayley Darke, Gabriel Dabscheck, Vicki A. Anderson, Katrina Williams, Kathryn N. North, Jonathan M. Payne

Published in: Molecular Autism | Issue 1/2022

Abstract

Background

Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics.

Methods

Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score ≥ 60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires.

Results

The study cohort comprised 68 children (3–15 years). Sixty-three per cent met the ADOS-2 ‘autism spectrum’ cut-off, and 34% exceeded the more stringent threshold for ‘autistic disorder’ on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by ‘insistence on sameness’ (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs.

Limitations

Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood.

Conclusions

Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management.

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American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013.

Lord C, Bishop SL. Recent advances in autism research as reflected in DSM-5 criteria for autism spectrum disorder. Annu Rev Clin Psychol. 2015;11:53–70. https://doi.org/10.1146/annurev-clinpsy-032814-112745.CrossRefPubMed

Constantino JN, Charman T. Diagnosis of autism spectrum disorder: reconciling the syndrome, its diverse origins, and variation in expression. Lancet Neurol. 2016;15(3):279–91. https://doi.org/10.1016/S1474-4422(15)00151-9.CrossRefPubMed

Grzadzinski R, Huerta M, Lord C. DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes. Mol Autism. 2013;4:12. https://doi.org/10.1186/s13229-016-0072-1.CrossRefPubMedPubMedCentral

Christensen DL, Braun KVN, Baio J, Bilder D, Charles J, Constantino JN, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2012. MMWR Surveill Summ. 2018;65(13):1–23. https://doi.org/10.15585/mmwr.ss6513a1.CrossRefPubMedPubMedCentral

Brignell A, Morgan AT, Woolfenden S, Klopper F, May T, Sarkozy V, et al. A systematic review and meta-analysis of the prognosis of language outcomes for individuals with autism spectrum disorder. Autism Dev Lang Impair. 2018;3:1–19. https://doi.org/10.1177/2396941518767610.CrossRef

Salazar F, Baird G, Chandler S, Tseng E, O’sullivan T, Howlin P, et al. Co-occurring psychiatric disorders in preschool and elementary school-aged children with autism spectrum disorder. J Autism Dev Disord. 2015;45(8):2283–94. https://doi.org/10.1007/s10803-015-2361-5.CrossRefPubMed

Geschwind DH, State MW. Gene hunting in autism spectrum disorder: on the path to precision medicine. Lancet Neurol. 2015;14(11):1109–20. https://doi.org/10.1016/S1474-4422(15)00044-7.CrossRefPubMedPubMedCentral

Myers SM, Challman TD, Bernier R, Bourgeron T, Chung WK, Constantino JN, et al. Insufficient evidence for “autism-specific” genes. Am J Hum Genet. 2020;106(5):587–95. https://doi.org/10.1016/j.ajhg.2020.04.004.CrossRefPubMedPubMedCentral

10.

Yuen RK, Szatmari P, Vorstman JA. The genetics of autism spectrum disorders. Autism and the pervasive developmental disorders: Cambridge, United Kingdom: Cambridge University Press; 2019. p. 112–28.

11.

Constantino JN. Deconstructing autism: from unitary syndrome to contributory developmental endophenotypes. Int Rev Psychiatry. 2018;30(1):18–24. https://doi.org/10.1080/09540261.2018.1433133.CrossRefPubMedPubMedCentral

12.

Patel J, Lukkes JL, Shekhar A. Overview of genetic models of autism spectrum disorders. Progress in brain research. 241: Elsevier; 2018. p. 1–36.

13.

Molosh AI, Shekhar A. Neurofibromatosis type 1 as a model system to study molecular mechanisms of autism spectrum disorder symptoms. Progress in brain research. 241: Elsevier; 2018. p. 37–62.

14.

Garg S, Green J. Studying child development in genetic models of ASD. Progress in brain research. 241: Elsevier; 2018. p. 159–92.

15.

Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A. 2010;152A(2):327–32. https://doi.org/10.1002/ajmg.a.33139.CrossRefPubMed

16.

Korf BR, Wayne H, Patterson MC, TePas E. Neurofibromatosis type 1 (NF1): pathogenesis, clinical features, and diagnosis. UpToDate, Waltham, MA.: UpToDate Retrieved from www.uptodate.com; 2015.

17.

Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet. 2014;94(5):677–94. https://doi.org/10.1016/j.ajhg.2014.03.018.CrossRefPubMedPubMedCentral

18.

Sato A. mTOR, a potential target to treat autism spectrum disorder. CNS Neurol Disord Drug Targets. 2016;15(5):533–43. https://doi.org/10.2174/1871527315666160413120638.CrossRefPubMedPubMedCentral

19.

Eissa N, Al-Houqani M, Sadeq A, Ojha SK, Sasse A, Sadek B. Current enlightenment about etiology and pharmacological treatment of autism spectrum disorder. Front Neurosci. 2018;12:304. https://doi.org/10.3389/fnins.2018.00304.CrossRefPubMedPubMedCentral

20.

Loth E, Murphy DG, Spooren W. Defining precision medicine approaches to autism spectrum disorders: concepts and challenges. Front Psychiatry. 2016;7:188. https://doi.org/10.2174/1871527315666160413120638.CrossRefPubMedPubMedCentral

21.

Morris SM, Acosta MT, Garg S, Green J, Huson S, Legius E, et al. Disease burden and symptom structure of autism in neurofibromatosis type 1: a study of the International NF1-ASD Consortium Team (INFACT). JAMA Psychiat. 2016;73(12):1276–84. https://doi.org/10.1001/jamapsychiatry.2016.2600.CrossRef

22.

Adviento B, Corbin IL, Widjaja F, Desachy G, Enrique N, Rosser T, et al. Autism traits in the RASopathies. J Med Genet. 2014;51(1):10–20. https://doi.org/10.1136/jmedgenet-2013-101951.CrossRefPubMed

23.

Plasschaert E, Descheemaeker MJ, Van Eylen L, Noens I, Steyaert J, Legius E. Prevalence of autism spectrum disorder symptoms in children with neurofibromatosis type 1. Am J Med Genet B. 2015;168(1):72–80. https://doi.org/10.1002/ajmg.b.32280.CrossRef

24.

Walsh KS, Velez JI, Kardel PG, Imas DM, Muenke M, Packer RJ, et al. Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1. Dev Med Child Neurol. 2013;55(2):131–8. https://doi.org/10.1111/dmcn.12038.CrossRefPubMed

25.

Garg S, Lehtonen A, Huson SM, Emsley R, Trump D, Evans DG, et al. Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population-based study. Dev Med Child Neurol. 2013;55(2):139–45. https://doi.org/10.1111/dmcn.12043.CrossRefPubMed

26.

Payne JM, Walsh KS, Pride NA, Haebich KM, Maier A, Chisholm A, et al. Social skills and autism spectrum disorder symptoms in children with neurofibromatosis type 1: evidence for clinical trial outcomes. Dev Med Child Neurol. 2020;62(7):813–9. https://doi.org/10.1111/dmcn.14517.CrossRefPubMed

27.

Chisholm AK, Anderson VA, Pride NA, Malarbi S, North KN, Payne JM. Social function and autism spectrum disorder in children and adults with neurofibromatosis type 1: a systematic review and meta-analysis. Neuropsychol Rev. 2018;28(3):317–40. https://doi.org/10.1007/s11065-018-9380-x.CrossRefPubMed

28.

Eijk S, Mous SE, Dieleman GC, Dierckx B, Rietman AB, de Nijs PFA, et al. Autism spectrum disorder in an unselected cohort of children with neurofibromatosis type 1 (NF1). J Autism Dev Disord. 2018;48(7):2278–85. https://doi.org/10.1007/s10803-018-3478-0.CrossRefPubMedPubMedCentral

29.

Garg S, Green J, Leadbitter K, Emsley R, Lehtonen A, Evans DG, et al. Neurofibromatosis type 1 and autism spectrum disorder. Pediatrics. 2013;132(6):e1642–8. https://doi.org/10.1542/peds.2013-1868.CrossRefPubMed

30.

Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014;383(9920):896–910. https://doi.org/10.1016/S0140-6736(13)61539-1.CrossRefPubMed

31.

May T, Brignell A, Williams K. Autism spectrum disorder prevalence in children aged 12–13 years from the Longitudinal Study of Australian Children. Autism Res. 2020;13(5):821–7. https://doi.org/10.1002/aur.2286.CrossRefPubMed

32.

Falkmer T, Anderson K, Falkmer M, Horlin C. Diagnostic procedures in autism spectrum disorders: a systematic literature review. Eur Child Adolesc Psychiatry. 2013;22(6):329–40. https://doi.org/10.1007/s00787-013-0375-0.CrossRefPubMed

33.

Lord C, Rutter M, DiLavore P, Risi S, Gotham K, Bishop S. Autism Diagnostic Observation Schedule-2nd edition (ADOS-2): Los Angeles. CA: Western Psychological Corporation; 2012.

34.

Le Couteur A, Lord C, Rutter M. The Autism Diagnostic Interview-Revised (ADI-R): Los Angeles, CA: Western Psychological Services; 2003.

35.

Garg S, Plasschaert E, Descheemaeker MJ, Huson S, Borghgraef M, Vogels A, et al. Autism spectrum disorder profile in neurofibromatosis type 1. J Autism Dev Disord. 2015;45(6):1649–57. https://doi.org/10.1007/s10803-014-2321-5.CrossRefPubMed

36.

Garg S, Heuvelman H, Huson S, Tobin H, Green J. Sex bias in autism spectrum disorder in neurofibromatosis type 1. J Neurodev Disord. 2016;8(26):1–8. https://doi.org/10.1186/s11689-016-9159-4.CrossRef

37.

Geoffray MM, Falissard B, Green J, Kerr B, Evans DG, Huson S, et al. Autism spectrum disorder symptom profile across the RASopathies. Front Psychiatry. 2021;11: 585700. https://doi.org/10.3389/fpsyt.2020.585700.CrossRefPubMedPubMedCentral

38.

Aoki Y, Niihori T, Inoue S-i, Matsubara Y. Recent advances in RASopathies. J Hum Genet. 2016;61(1):33–9. https://doi.org/10.1038/jhg.2015.114.CrossRefPubMed

39.

Rauen KA. The rasopathies. Annu Rev Genomics Hum Genet. 2013;14:355–69. https://doi.org/10.1146/annurev-genom-091212-153523.CrossRefPubMedPubMedCentral

40.

Hus V, Gotham K, Lord C. Standardizing ADOS domain scores: separating severity of social affect and restricted and repetitive behaviors. J Autism Dev Disord. 2014;44(10):2400–12. https://doi.org/10.1007/s10803-012-1719-1.CrossRefPubMedPubMedCentral

41.

Morotti H, Mastel S, Keller K, Barnard RA, Hall T, O'Roak BJ, et al. The association of neurofibromatosis and autism symptomatology is confounded by behavioral problems. medRxiv. 2019. https://doi.org/10.1101/2019.12.20.19015420

42.

Fombonne E, Morotti H, Mastel S, Keller K, Barnard RA, Hall T, et al. Autism questionnaire scores do not only rise because of autism. Dev Med Child Neurol. 2021;63(2):235–6. https://doi.org/10.1111/dmcn.14725.CrossRefPubMed

43.

Morris SM, Acosta MT, Garg S, Green J, Legius E, North K, et al. Autism in neurofibromatosis type 1: misuse of covariance to dismiss autistic trait burden. Dev Med Child Neurol. 2021;63(2):233–4. https://doi.org/10.1111/dmcn.14653.CrossRefPubMed

44.

Klein-Tasman BP. Are the autism symptoms in neurofibromatosis type 1 actually autism? Dev Med Child Neurol. 2021;63(2):132. https://doi.org/10.1111/dmcn.14597.CrossRefPubMed

45.

Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008;47(8):921–9. https://doi.org/10.1097/CHI.0b013e318179964f.CrossRefPubMed

46.

Aldridge FJ, Gibbs VM, Schmidhofer K, Williams M. Investigating the clinical usefulness of the Social Responsiveness Scale (SRS) in a tertiary level, autism spectrum disorder specific assessment clinic. J Autism Dev Disord. 2012;42(2):294–300. https://doi.org/10.1007/s10803-011-1242-9.CrossRefPubMed

47.

Happe F, Ronald A, Plomin R. Time to give up on a single explanation for autism. Nat Neurosci. 2006;9(10):1218–20. https://doi.org/10.1038/nn1770.CrossRefPubMed

48.

Pride NA, North KN. The cognitive profile of NF1 children: therapeutic implications. Neurofibromatosis type 1: Springer; 2012. p. 55–69.

49.

Wang DL, Smith KB, Esparza S, Leigh FA, Muzikansky A, Park ER, et al. Emotional functioning of patients with neurofibromatosis tumor suppressor syndrome. Genet Med. 2012;14(12):977–82. https://doi.org/10.1038/gim.2012.85.CrossRefPubMedPubMedCentral

50.

Cholemkery H, Mojica L, Rohrmann S, Gensthaler A, Freitag CM. Can autism spectrum disorders and social anxiety disorders be differentiated by the Social Responsiveness Scale in children and adolescents? J Autism Dev Disord. 2014;44(5):1168–82. https://doi.org/10.1007/s10803-013-1979-4.CrossRefPubMed

51.

Grzadzinski R, Dick C, Lord C, Bishop S. Parent-reported and clinician-observed autism spectrum disorder (ASD) symptoms in children with attention deficit/hyperactivity disorder (ADHD): implications for practice under DSM-5. Mol Autism. 2016;7(1):1–12. https://doi.org/10.1186/s13229-016-0072-1.CrossRef

52.

Haebich KM, Pride NA, Walsh KS, Chisholm A, Rouel M, Maier A, et al. Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study. BMJ Open. 2019;9(9): e030601. https://doi.org/10.1136/bmjopen-2019-030601.CrossRefPubMedPubMedCentral

53.

Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol. 1988;45(5):575–8.

54.

American Psychiatric Association. Diagnostic and statistical manual of mental disorders-Fourth edition-Text revision (DSM-IV-TR): American Psychiatric Pub; 2000.

55.

Gotham K, Pickles A, Lord C. Standardizing ADOS scores for a measure of severity in autism spectrum disorders. J Autism Dev Disord. 2009;39(5):693–705. https://doi.org/10.1007/s10803-008-0674-3.CrossRefPubMed

56.

Bal VH, Lord C. Replication of standardized ADOS domain scores in the Simons Simplex Collection. Autism Res. 2015;8(5):583–92. https://doi.org/10.1002/aur.1474.CrossRefPubMedCentral

57.

de Bildt A, Oosterling IJ, van Lang ND, Sytema S, Minderaa RB, van Engeland H, et al. Standardized ADOS scores: measuring severity of autism spectrum disorders in a Dutch sample. J Autism Dev Disord. 2011;41(3):311–9. https://doi.org/10.1007/s10803-010-1057-0.CrossRefPubMed

58.

Wechsler D. Wechsler Preschool and Primary Scale of Intelligence-4th edition (WPPSI-IV). San Antonio, Tx: Pearson; 2012.

59.

Wechsler D. Wechsler Intelligence Scale for Children-5th edition (WISC-V): Bloomington, MN: Pearson; 2014.

60.

Bornstein MH, Hahn C-S, Suwalsky JT, Haynes OM. Socioeconomic status, parenting, and child development: The Hollingshead Four-Factor Index of Social Status and The Socioeconomic Index of Occupations: Lawrence Erlbaum Associates Publishers; 2003.

61.

Constantino JN, Gruber CP. Social Responsiveness Scale, Second edition. Los Angeles: Western Psychological Services; 2012.

62.

Conners CK. Conners’ Rating Scales-Revised. New York: Multi-Health Systems Inc.; 1997.

63.

Conners CK. Conners. 3rd ed. Toronto: Multi-Health Systems Inc; 2009.

64.

Achenbach TM, Rescorla LA. Child Behavior Checklist for ages 1 1/2–5: ASEBA. University of Vermont; 2000.

65.

Achenbach TM, Rescorla LA. Manual for the ASEBA school-age forms and profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, and Families; 2001.

66.

Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers. 2017;3:17004. https://doi.org/10.1038/nrdp.2017.4.CrossRefPubMed

67.

Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed: Hillsdale, NJ: Lawrence Erlbaum Associates; 1988.

68.

Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57(1):289–300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.x.CrossRef

69.

Hinkle DE, Wiersma W, Jurs SG. Applied statistics for the behavioral sciences: Houghton Mifflin College Division; 2003.

70.

Vivanti G, Volkmar FR. National guideline for the assessment and diagnosis of autism spectrum disorders in Australia. J Autism Dev Disord. 2020;50:2252–4. https://doi.org/10.1007/s10803-019-03937-x.CrossRef

71.

Randall M, Egberts KJ, Samtani A, Scholten RJ, Hooft L, Livingstone N, et al. Diagnostic tests for autism spectrum disorder (ASD) in preschool children. Cochrane Database Syst Rev. 2018;7:CD009044. https://doi.org/10.1002/14651858.CD009044.pub2

72.

Noll RB, Reiter-Purtill J, Moore BD, Schorry EK, Lovell AM, Vannatta K, et al. Social, emotional, and behavioral functioning of children with NF1. Am J Med Genet A. 2007;143A(19):2261–73. https://doi.org/10.1002/ajmg.a.31923.CrossRefPubMed

73.

Lewis AK, Porter MA, Williams TA, Bzishvili S, North KN, Payne JM. Facial emotion recognition, face scan paths, and face perception in children with neurofibromatosis type 1. Neuropsychology. 2017;31(4):361–70. https://doi.org/10.1037/neu0000340.CrossRefPubMed

74.

Lewis AK, Porter MA, Williams TA, Bzishvili S, North KN, Payne JM. Attention to faces in social context in children with neurofibromatosis type 1. Dev Med Child Neurol. 2019;61(2):174–80. https://doi.org/10.1111/dmcn.13928.CrossRefPubMed

75.

Cuccaro ML, Shao Y, Grubber J, Slifer M, Wolpert CM, Donnelly SL, et al. Factor analysis of restricted and repetitive behaviors in autism using the Autism Diagnostic Interview-R. Child Psychiatry Hum Dev. 2003;34(1):3–17. https://doi.org/10.1023/A:1025321707947.CrossRefPubMed

76.

Szatmari P, Georgiades S, Bryson S, Zwaigenbaum L, Roberts W, Mahoney W, et al. Investigating the structure of the restricted, repetitive behaviours and interests domain of autism. J Child Psychol Psychiatry. 2006;47(6):582–90. https://doi.org/10.1111/j.1469-7610.2005.01537.x.CrossRefPubMed

77.

Bishop SL, Hus V, Duncan A, Huerta M, Gotham K, Pickles A, et al. Subcategories of restricted and repetitive behaviors in children with autism spectrum disorders. J Autism Dev Disord. 2013;43(6):1287–97. https://doi.org/10.1007/s10803-012-1671-0.CrossRefPubMedPubMedCentral

78.

Gotham K, Bishop SL, Hus V, Huerta M, Lund S, Buja A, et al. Exploring the relationship between anxiety and insistence on sameness in autism spectrum disorders. Autism Res. 2013;6(1):33–41. https://doi.org/10.1002/aur.1263.CrossRefPubMed

79.

Bishop SL, Richler J, Lord C. Association between restricted and repetitive behaviors and nonverbal IQ in children with autism spectrum disorders. Child Neuropsychol. 2006;12(4–5):247–67. https://doi.org/10.1080/09297040600630288.CrossRefPubMed

80.

Payne JM, Hyman SL, Shores EA, North KN. Assessment of executive function and attention in children with neurofibromatosis type 1: relationships between cognitive measures and real-world behavior. Child Neuropsychol. 2011;17(4):313–29. https://doi.org/10.1080/09297049.2010.542746.CrossRefPubMed

81.

Walsh KS, del Castillo A, Kennedy T, Karim AI, Semerjian C. A review of psychological, social, and behavioral functions in the RASopathies. J Pediatr Neuropsychol. 2020;6(3):131–42. https://doi.org/10.1007/s40817-020-00088-1.CrossRef

82.

Boyd BA, McBee M, Holtzclaw T, Baranek GT, Bodfish JW. Relationships among repetitive behaviors, sensory features, and executive functions in high functioning autism. Res Autism Spectr Disord. 2009;3(4):959–66. https://doi.org/10.1016/j.rasd.2009.05.003.CrossRefPubMedPubMedCentral

83.

Baribeau DA, Vigod S, Pullenayegum E, Kerns CM, Mirenda P, Smith IM, et al. Co-occurring trajectories of anxiety and insistence on sameness behaviour in autism spectrum disorder. Br J Psychiatry. 2021;218(1):20–7. https://doi.org/10.1192/bjp.2020.127.CrossRefPubMed

84.

Cholemkery H, Kitzerow J, Rohrmann S, Freitag CM. Validity of the social responsiveness scale to differentiate between autism spectrum disorders and disruptive behaviour disorders. Eur Child Adolesc Psychiatry. 2014;23(2):81–93. https://doi.org/10.1007/s00787-013-0427-5.CrossRefPubMed

85.

Hus V, Bishop S, Gotham K, Huerta M, Lord C. Factors influencing scores on the social responsiveness scale. J Child Psychol Psychiatry. 2013;54(2):216–24. https://doi.org/10.1111/j.1469-7610.2012.02589.x.CrossRefPubMed

86.

Mody M, Belliveau JW. Speech and language impairments in autism: insights from behavior and neuroimaging. N Am J Med Sci. 2013;5(3):157–61. https://doi.org/10.7156/v5i3p157.CrossRef

87.

Cochet H, Byrne RW. Communication in the second and third year of life: relationships between nonverbal social skills and language. Infant Behav Dev. 2016;44:189–98. https://doi.org/10.1016/j.infbeh.2016.07.003.CrossRefPubMed

88.

Anderson DK, Liang JW, Lord C. Predicting young adult outcome among more and less cognitively able individuals with autism spectrum disorders. J Child Psychol Psychiatry. 2014;55(5):485–94. https://doi:https://doi.org/10.1111/jcpp.12178

89.

Evans DW, Leckman JF, Carter A, Reznick JS, Henshaw D, King RA, et al. Ritual, habit, and perfectionism: the prevalence and development of compulsive-like behavior in normal young children. Child Dev. 1997;68(1):58–68. https://doi.org/10.2307/1131925.CrossRefPubMed

90.

Vivanti G, Prior M, Williams K, Dissanayake C. Predictors of outcomes in autism early intervention: why don’t we know more? Front Pediatr. 2014;2:58. https://doi.org/10.3389/fped.2014.00058.CrossRefPubMedPubMedCentral

91.

Howlin P, Magiati I, Charman T. Systematic review of early intensive behavioral interventions for children with autism. Am J Intellect Dev Disabil. 2009;114(1):23–41. https://doi.org/10.1352/2009.114:23-41.CrossRefPubMed

92.

Fuentes J, Hervás A, Howlin P. ESCAP practice guidance for autism: a summary of evidence-based recommendations for diagnosis and treatment. Eur Child Adolesc Psychiatry. 2021;30(6):961–84. https://doi.org/10.1007/s00787-020-01587-4.CrossRefPubMed

93.

Darling SJ, Goods M, Ryan NP, Chisholm AK, Haebich K, Payne JM. Behavioral intervention for social challenges in children and adolescents: a systematic review and meta-analysis. JAMA Pediatr. 2021;175(12):e213982. https://doi.org/10.1001/jamapediatrics.2021.3982.

94.

Zachor DA, Ben-Itzchak E. Variables affecting outcome of early intervention in autism spectrum disorder. J Pediatr Neurol. 2017;15(3):129–33. https://doi.org/10.1055/s-0037-1601444.CrossRef

95.

Havdahl KA, Bal VH, Huerta M, Pickles A, Øyen A-S, Stoltenberg C, et al. Multidimensional influences on autism symptom measures: implications for use in etiological research. J Am Acad Child Adolesc Psychiatry. 2016;55(12):1054–63. https://doi.org/10.1016/j.jaac.2016.09.490.CrossRefPubMedPubMedCentral

96.

Bettegowda C, Upadhayaya M, Evans DG, Kim A, Mathios D, Hanemann CO, et al. Genotype-phenotype correlations in neurofibromatosis and their potential clinical use. Neurology. 2021;97(7 Supplement 1):S91–8. https://doi.org/10.1212/WNL.0000000000012436.CrossRefPubMed

97.

Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, et al. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019;51(3):431–44. https://doi.org/10.1038/s41588-019-0344-8.CrossRefPubMedPubMedCentral

98.

Jones RM, Risi S, Wexler D, Anderson D, Corsello C, Pickles A, et al. How interview questions are placed in time influences caregiver description of social communication symptoms on the ADI-R. J Child Psychol Psychiatry. 2015;56(5):577–85. https://doi.org/10.1111/jcpp.12325.CrossRefPubMed

99.

Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J. Autism spectrum disorder. Lancet. 2018;392(10146):508–20. https://doi.org/10.1016/S0140-6736(18)31129-2.CrossRefPubMedPubMedCentral

100.

Zwaigenbaum L, Bauman ML, Choueiri R, Kasari C, Carter A, Granpeesheh D, et al. Early intervention for children with autism spectrum disorder under 3 years of age: recommendations for practice and research. Pediatrics. 2015;136(Supplement 1):S60–81. https://doi.org/10.1542/peds.2014-3667E.CrossRefPubMed

Title: Delineating the autistic phenotype in children with neurofibromatosis type 1
Authors: Anita K. Chisholm
Kristina M. Haebich
Natalie A. Pride
Karin S. Walsh
Francesca Lami
Alex Ure
Tiba Maloof
Amanda Brignell
Melissa Rouel
Yael Granader
Alice Maier
Belinda Barton
Hayley Darke
Gabriel Dabscheck
Vicki A. Anderson
Katrina Williams
Kathryn N. North
Jonathan M. Payne
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Attention Deficit Hyperactivity Disorder
Neurofibromatosis Type 1
Attention Deficit Hyperactivity Disorder
Published in: Molecular Autism / Issue 1/2022
Electronic ISSN: 2040-2392
DOI: https://doi.org/10.1186/s13229-021-00481-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Delineating the autistic phenotype in children with neurofibromatosis type 1

Abstract

Background

Methods

Results

Limitations

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Limitations

Conclusions

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