In light of the proliferation of recent research into social function in neurofibromatosis type 1 (NF1), a systematic review and meta-analysis is required to synthesise data and place findings within the context of a theoretical framework. This paper reviews findings from research into social function and autism spectrum disorder (ASD) in children and adults with NF1 and integrates these findings with the Socio-Cognitive Integration Abilities Model (SOCIAL). It also critically appraises links between social outcomes, internal and external factors moderating social functioning, cognitive domains implicated in social functioning, and underlying neural pathology in NF1. A systematic literature search conducted in MedLine (Ovid), PsycINFO (Ovid), Embase (Ovid), and PubMed electronic databases yielded 35 papers that met inclusion criteria for the systematic review. Out of these papers, 22 papers provided sufficient data for meta-analysis. Findings from this review and meta-analysis provide evidence that children and adults with NF1 exhibit significantly higher prevalence and severity of social dysfunction and ASD symptomatology. To date, very few studies have examined social cognition in NF1 but results indicate the presence of both perceptual and higher-level impairments in this population. The results of this review also provide support for age, gender, and comorbid ADHD as moderating factors for social outcomes in NF1. Suggestions for future research are offered to further our understanding of the social phenotype in NF1 and to facilitate the development of targeted interventions.

Aim We examined key features of two outcome measures for social dysfunction and autism spectrum disorder traits, the Social Responsiveness Scale, Second Edition (SRS‐2) and the Social Skills Improvement System – Rating Scales (SSIS‐RS), in children with neurofibromatosis type 1 (NF1). The aim of the study was to provide objective evidence as to which behavioural endpoint should be used in clinical trials. Method Cross‐sectional behavioural and demographic data were pooled from four paediatric NF1 tertiary referral centres in Australia and the United States (N=122; 65 males, 57 females; mean age [SD] 9y 2mo [3y], range 3–15y). Results Distributions of SRS‐2 and SSIS‐RS scores were unimodal and both yielded deficits, with a higher proportion of severely impaired scores on the SRS‐2 (16.4%) compared to the SSIS‐RS (8.2%). Pearson’s product‐moment correlations revealed that both questionnaires were highly related to each other (r=−0.72, p<0.001) and to measures of adaptive social functioning (both p<0.001). Both questionnaires were significantly related to attention‐deficit/hyperactivity disorder symptoms, but only very weakly associated with intelligence. Interpretation The SRS‐2 and SSIS‐RS capture social dysfunction associated with NF1, suggesting both may be suitable choices for assessing social outcomes in this population in a clinical trial. However, careful thought needs to be given to the nature of the intervention when selecting either as a primary endpoint. What this paper adds The Social Responsiveness Scale, Second Edition yielded a large deficit relative to population norms. The Social Skills Improvement System – Rating Scales yielded a moderate deficit relative to population norms. Both scales were highly correlated, suggesting that they are measuring a unitary construct.

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.