Developmental trajectories in infants and pre-school children with Neurofibromatosis 1.

Publisher: BioMed Central Country of Publication: England NLM ID: 101534222 Publication Model: Electronic Cited Medium: Internet ISSN: 2040-2392 (Electronic) NLM ISO Abbreviation: Mol Autism Subsets: MEDLINE

Original Publication: [London] : BioMed Central

Neurofibromatosis 1* ; Cognition*; Humans ; Infant ; Female ; Male ; Child, Preschool ; Child Development ; Attention Deficit Disorder with Hyperactivity/diagnosis ; Prospective Studies ; Autistic Disorder/diagnosis

Background: Children with Neurofibromatosis 1 (NF1) show cognitive, behavioural and social differences compared to their peers. However, the age and sequence at which these differences begin to emerge is not fully understood. This prospective cohort study examines the cognitive, behavioural, ADHD trait and autism symptom development in infant and pre-school children with NF1 compared with typically developing (TD) children without a family history of neurodevelopmental conditions.
Methods: Data from standardised tests was gathered at 5, 10, 14, 24 and 36 months of age (NF1 n = 35, TD n = 29). Developmental trajectories of cognitive (Mullen Scales of Early Learning, MSEL) and adaptive behavioural (Vineland Adaptive Behavior Scales, VABS) development from 5 to 36 months were analysed using linear mixed modelling. Measures of ADHD (Child Behavior Checklist) and autism traits (ADOS-2, BOSA-MV and ADI-R) were assessed at 24 and 36 months.
Results: The developmental trajectory of cognitive skills (all domains of the MSEL) and behavioural skills (four domains of the VABS) differed significantly between NF1 and TD groups. Post-hoc tests demonstrated that the NF1 participants scored significantly lower than TD participants at 24 months on all MSEL and VABS domains. The NF1 cohort demonstrated higher mean autism and ADHD traits at 24 months and 14% of the NF1 cohort met a research diagnostic classification for autism at 36 months.
Limitations: The study has a relatively small sample size due to variable retention and rolling recruitment. Due to limitations imposed by the COVID-19 pandemic, we utilised the Brief Observation of Symptoms of Autism for Minimally Verbal children (BOSA-MV) for some participants, which was administered online and may not gather as accurate a picture of traits as ADOS-2. The BOSA-MV was utilised for 41% of participants with NF1 at 36 months compared to 11% at 24 months. This may explain the reduction in the percentage of children with NF1 that met autism criteria at 36 months.
Conclusions: By 24 months of age, the NF1 cohort show lower cognitive skills and adaptive behaviour and higher levels of autism and ADHD traits as compared to TD children. This has implications for developmental monitoring and referral for early interventions.
Trial Registration: Not applicable.
(© 2024. The Author(s).)

Am J Med Genet A. 2010 Feb;152A(2):327-32. (PMID: 20082463)
J Child Psychol Psychiatry. 2021 May;62(5):610-630. (PMID: 33432656)
J Neurodev Disord. 2021 May 28;13(1):22. (PMID: 34049498)
Front Behav Neurosci. 2022 Jul 06;16:900981. (PMID: 35874653)
J Pediatr. 2013 Nov;163(5):1479-83.e1. (PMID: 23910685)
Mol Autism. 2015 Jun 04;6:32. (PMID: 26045943)
J Pediatr. 2017 Apr;183:141-146.e1. (PMID: 28162768)
J Pediatr Psychol. 2022 Feb 14;47(2):180-188. (PMID: 34664663)
Dev Med Child Neurol. 2013 Feb;55(2):111-125. (PMID: 22934576)
Front Psychiatry. 2021 Jan 15;11:585700. (PMID: 33519543)
Neuropsychol Rev. 2018 Sep;28(3):317-340. (PMID: 30097761)
Dev Med Child Neurol. 2013 Feb;55(2):139-145. (PMID: 23163236)
Biol Psychiatry. 2013 Aug 1;74(3):189-94. (PMID: 23374640)
J Autism Dev Disord. 2000 Jun;30(3):205-23. (PMID: 11055457)
Ann Neurol. 2013 Feb;73(2):309-15. (PMID: 23225063)
Front Neurol. 2020 May 05;11:368. (PMID: 32431664)
Res Dev Disabil. 2014 Oct;35(10):2495-504. (PMID: 24995687)
J Child Neurol. 2013 Dec;28(12):1689-93. (PMID: 23112244)
Dev Psychopathol. 2015 May;27(2):425-42. (PMID: 25997763)
J Autism Dev Disord. 2015 Jul;45(7):2267-73. (PMID: 25676685)
J Int Neuropsychol Soc. 2014 Jan;20(1):88-98. (PMID: 24229851)
J Neurodev Disord. 2016 Jul 26;8:26. (PMID: 27516813)
J Autism Dev Disord. 2022 Dec;52(12):5383-5394. (PMID: 34914016)
Mol Autism. 2017 Nov 23;8:62. (PMID: 29204259)
J Child Neurol. 2012 May;27(5):641-4. (PMID: 22190506)
J Pediatr. 2011 Apr;158(4):660-5. (PMID: 21094952)
Front Psychiatry. 2024 Apr 29;15:1378593. (PMID: 38742132)
Hum Genet. 2022 Feb;141(2):177-191. (PMID: 34928431)
J Child Psychol Psychiatry. 2017 Dec;58(12):1330-1340. (PMID: 28393350)
J Am Acad Child Adolesc Psychiatry. 2006 Sep;45(9):1094-1103. (PMID: 16926617)
Front Psychol. 2022 Jul 22;13:795951. (PMID: 35936291)
J Clin Exp Neuropsychol. 2021 Mar;43(2):163-175. (PMID: 33685350)
J Autism Dev Disord. 2015 Jun;45(6):1649-57. (PMID: 25475362)
J Autism Dev Disord. 2021 Mar;51(3):973-993. (PMID: 32734422)
J Pediatr. 2015 Apr;166(4):1006-12.e1. (PMID: 25598303)
Int J Lang Commun Disord. 2018 Sep;53(5):1007-1020. (PMID: 30079576)
Sci Rep. 2017 Mar 06;7:43929. (PMID: 28262833)
Res Autism Spectr Disord. 2015 Dec 1;20:58-66. (PMID: 26779281)
J Autism Dev Disord. 2009 Sep;39(9):1305-20. (PMID: 19415479)
Biol Psychiatry. 2009 Jan 1;65(1):31-8. (PMID: 19064038)
Dev Med Child Neurol. 2020 Aug;62(8):977-984. (PMID: 32052421)
Ann Am Acad Pol Soc Sci. 2017 Nov;674(1):59-84. (PMID: 29563643)
Neurology. 2005 Oct 11;65(7):1037-44. (PMID: 16217056)
J Autism Dev Disord. 1994 Oct;24(5):659-85. (PMID: 7814313)
Genet Med. 2021 Aug;23(8):1506-1513. (PMID: 34012067)
J Pediatr Psychol. 2017 Mar 01;42(2):198-207. (PMID: 27189686)
Mol Autism. 2022 Dec 8;13(1):46. (PMID: 36482366)

Investigator: M Agyapong; T Bazelmans; L Dafner; M Ersoy; T Gliga; A Goodwin; R Haartsen; H Halkola; A Hendry; R Holman; S Kalwarowsky; S Lloyd-Fox; L Mason; N Narvekar; L Pirazzoli; C Taylor; G Vassallo; J Eelloo; DG Evans; S West; E Hupton; L Robinson; N Lakhani; B Wilson; D Osio; C Shaw-Smith; N Canham; S Sharif
Keywords: ADHD; Autism; Children; Cohort; NF1; Neurofibromatosis; Trajectories

Date Created: 20241015 Date Completed: 20241016 Latest Revision: 20241023

20241024

PMC11481376

10.1186/s13229-024-00621-5

39407332