Autism Spectrum Disorder in Neufibromatosis Type 1: Prevalence and characterisation of the phenotype

    Student thesis: Phd


    Autism Spectrum disorder (ASD) is a pervasive developmental disorder with a population prevalence of about 1%. The aetiology of ASD is complex and highly heterogeneous but the importance of a genetic contribution is well known. There is a growing body of interest in the study of ASD in genetic syndromes as one potential route to understanding the overall neurobiology of autism. Neurofibromatosis Type 1 (NF1) is a common autosomal dominant genetic disorder in which an association with ASD has been described. NF1 is an important monogenic disorder model to study in the context of ASD as its genetics, neurobiology and neuropathology are well understood and there are available candidate treatments that can specifically target the neurobiological pathway in the disorder.Using a two-phase approach in a large population based sample of children with NF1, the behavioural phenotype and the prevalence of ASD was studied. Study I found a population prevalence of autism symptomatology of 60% on parent-reported screening measures. In-depth phenotyping on a proportion of the Study I sample found ASD prevalence estimates of 25% ASD in the NF1 population. Detailed characterization of the NF1-ASD phenotype was carried out by comparing the NF1+ASD sample, to non-syndromic ASD. The NF1+ASD phenotype showed overall similarity to non-syndromic ASD but with improved eye contact, less repetitive behaviours and better language skills. Further the NF1+ASD sample was compared to the NF1 only sample-using parent reported Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). The results suggested significant group differences; discriminating behaviours between the groups include items relating to imaginative play, sharing, unusual preoccupations and sensory interests.These studies establish NF1 as a single gene model of syndromic autism. Detailed characterisation of the NF1+ASD phenotype shows marked similarities with non-syndromic ASD but also some differences. The neurobiology of NF1 is well understood and there are candidate treatments that have shown to reverse the underlying learning and social skills deficits in murine models. Studies of behavioural phenotypes of NF1 are therefore of crucial importance and can help illuminate the neurobiology of autism development. Furthermore targeted pharmacological interventions developed for symptoms NF1 may have some benefit for non-syndromic ASD as well.
    Date of Award31 Dec 2015
    Original languageEnglish
    Awarding Institution
    • The University of Manchester
    SupervisorJonathan Green (Supervisor) & Susan Huson (Supervisor)


    • Autism Spectrum Disorder
    • Neurofibromatosis Type 1

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