Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study

Kristina M Haebich; Natalie A Pride; Karin S Walsh; Anita Chisholm; Melissa Rouel; Alice Maier; Vicki Anderson; Belinda Barton; Tim Silk; Mayuresh Korgaonkar; Marc Seal; Francesca Lami; Jennifer Lorenzo; Katrina Williams; Gabriel Dabscheck; Caroline D Rae; Michael Kean; Kathryn N North; Jonathan M Payne

doi:10.1136/bmjopen-2019-030601

Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study

BMJ Open. 2019 Sep 26;9(9):e030601. doi: 10.1136/bmjopen-2019-030601.

Authors

Kristina M Haebich^{1

2}, Natalie A Pride^{3

4}, Karin S Walsh^{5

6}, Anita Chisholm^{1

2}, Melissa Rouel³, Alice Maier¹, Vicki Anderson^{1

2}, Belinda Barton^{3

4

7}, Tim Silk⁸, Mayuresh Korgaonkar⁹, Marc Seal¹⁰, Francesca Lami¹, Jennifer Lorenzo³, Katrina Williams¹¹, Gabriel Dabscheck¹², Caroline D Rae¹³, Michael Kean¹⁴, Kathryn N North^{2

15}, Jonathan M Payne^{16

2}

Affiliations

¹ Brain and Mind, Murdoch Children's Research Institute, Parkville, VIC, Australia.
² Department of Paediatrics, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Parkville, VIC, Australia.
³ Kids Neuroscience Centre, The Children's Hospital at Westmead, Westmead, NSW, Australia.
⁴ Discipline of Child and Adolescent Health, University of Sydney Medical School, Westmead, NSW, Australia.
⁵ Center for Neuroscience and Behavioral Medicine, Children's National Health System, Washington, DC, United States.
⁶ Departments of Pediatrics and Psychiatry, The George Washington University School of Medicine, Washington, DC, United States.
⁷ Children's Hospital Education Research Institute, The Children's Hospital at Westmead, Westmead, NSW, Australia.
⁸ School of Psychology, Deakin University, Burwood, VIC, Australia.
⁹ Brain Dynamics Centre, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
¹⁰ Developmental Imaging, Murdoch Children's Research Institute, Parkville, VIC, Australia.
¹¹ Department of Paediatrics, Monash University, Clayton, VIC, Australia.
¹² Department of Neurology, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
¹³ Neuroscience Research Australia, University of New South Wales, Randwick, NSW, Australia.
¹⁴ Imaging Department, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
¹⁵ Murdoch Children's Research Institute, Parkville, VIC, Australia.
¹⁶ Brain and Mind, Murdoch Children's Research Institute, Parkville, VIC, Australia jonathan.payne@mcri.edu.au.

Abstract

Introduction: Children with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD.

Methods and analysis: This is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3-15 years of age), 70 TD participants (3-15 years) and 35 children with idiopathic ASD (7-15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child's behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria.

Ethics and dissemination: This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.

Keywords: Autism spectrum disorder; Magnetic resonance imaging; Neurofibromatosis type 1; Social cognition; Social functioning.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Autism Spectrum Disorder / etiology*
Autism Spectrum Disorder / genetics
Autism Spectrum Disorder / physiopathology
Autism Spectrum Disorder / psychology
Autistic Disorder / psychology
Child
Child Behavior*
Child Development
Child, Preschool
Cognition*
Cross-Sectional Studies
Female
Humans
Male
Nervous System / physiopathology
Neurofibromatosis 1 / complications*
Neurofibromatosis 1 / physiopathology
Neurofibromatosis 1 / psychology
Phenotype*
Prospective Studies
Research Design
Social Behavior*