Delineating the autistic phenotype in children with neurofibromatosis type 1

Molecular Autism

Karin S. Walsh¹  Yael Granader¹  Tiba Maloof²  Melissa Rouel³  Natalie A. Pride³  Belinda Barton⁴  Hayley Darke⁵  Alice Maier⁶  Kathryn N. North⁶  Kristina M. Haebich⁶  Francesca Lami⁶  Katrina Williams⁷  Vicki A. Anderson⁸  Gabriel Dabscheck⁸  Jonathan M. Payne⁸  Anita K. Chisholm⁸  Amanda Brignell⁹  Alex Ure^1,10 

[1] Center for Neuroscience and Behavioral Medicine, Children’s National Hospital, Michigan Avenue NW, 20310, Washington, DC, USA;Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, 3010, Parkville, VIC, Australia;The Royal Children’s Hospital, 50 Flemington Road, 3052, Parkville, VIC, Australia;Kids Neuroscience Centre, The Children’s Hospital at Westmead, 178A Hawkesbury Road, 2145, Westmead, NSW, Australia;Kids Neuroscience Centre, The Children’s Hospital at Westmead, 178A Hawkesbury Road, 2145, Westmead, NSW, Australia;Sydney Medical School, University of Sydney, 2050, Camperdown, NSW, Australia;Children’s Hospital Education Research Institute, The Children’s Hospital at Westmead, 178A Hawkesbury Road, 2145, Westmead, NSW, Australia;Murdoch Children’s Research Institute, 50 Flemington Road, 3052, Parkville, VIC, Australia;Murdoch Children’s Research Institute, 50 Flemington Road, 3052, Parkville, VIC, Australia;Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, 3010, Parkville, VIC, Australia;Murdoch Children’s Research Institute, 50 Flemington Road, 3052, Parkville, VIC, Australia;Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, 3010, Parkville, VIC, Australia;Department of Paediatrics, School of Clinical Sciences, Monash University, 246 Clayton Road, 3168, Clayton, VIC, Australia;Developmental Paediatrics, Monash Children’s Hospital, 246 Clayton Road, 3168, Clayton, VIC, Australia;Murdoch Children’s Research Institute, 50 Flemington Road, 3052, Parkville, VIC, Australia;Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, 3010, Parkville, VIC, Australia;The Royal Children’s Hospital, 50 Flemington Road, 3052, Parkville, VIC, Australia;Murdoch Children’s Research Institute, 50 Flemington Road, 3052, Parkville, VIC, Australia;Department of Paediatrics, School of Clinical Sciences, Monash University, 246 Clayton Road, 3168, Clayton, VIC, Australia;Murdoch Children’s Research Institute, 50 Flemington Road, 3052, Parkville, VIC, Australia;Department of Paediatrics, School of Clinical Sciences, Monash University, 246 Clayton Road, 3168, Clayton, VIC, Australia;Developmental Paediatrics, Monash Children’s Hospital, 246 Clayton Road, 3168, Clayton, VIC, Australia;

关键词: Autism;    Autistic behaviours;    Autism Diagnostic Interview-Revised (ADI-R);    Autism Diagnostic Observation Schedule-Second Edition (ADOS-2);    Neurofibromatosis type 1;   

DOI  :  10.1186/s13229-021-00481-3

来源: Springer

【 摘 要 】

BackgroundExisting 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.MethodsParticipants 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.ResultsThe 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.LimitationsLack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood.ConclusionsFindings 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.

【 授权许可】

CC BY