Trajectories of motor development in Neurofibromatosis 1 in the preschool period

点击翻译按钮获取中文摘要

Neurofibromatosis 1 is a common autosomal dominant single gene neurodevelopmental disorder, with birth incidence of 1:2700. It is caused by a mutation of the NF1 gene on chromosome 17q11.2, which has an important role in intracellular signalling, learning and synaptic plasticity. Motor, cognitive and learning problems are common in NF1 and there is a high prevalence of both autism spectrum disorder (ASD) of approximately 25% and Attention Deficit Hyperactivity Disorder (ADHD) of about 50% in NF1. Motor difficulties including gross and fine motor impairments, balance and coordination difficulties are commonly reported in NF1. These impairments impact quality of life, academic functioning, peer, and social relationships. Emerging research suggests that motor impairments may be a component of the ASD phenotype. Although motor impairments are commonly reported in NF1, the trajectory of motor development is not well understood. Understanding the trajectory of development will be important for early diagnosis and intervention. Understanding the trajectory of motor development to identify early signs may help use develop early rehabilitation approaches, which could in turn ameliorate the emergence of motor, cognitive and behavioural difficulties seen in NF1.This doctoral project is in collaboration with Nerve Tumours UK as our charity industry partner (https://nervetumours.org.uk/). The aims of this study will be (i) to determine the trajectories of motor development in NF1 infants from 5months to 3 years using the Mullen Scale of Early learning, and parent reported data and compare it to low-risk controls (iii) examine the trajectory of objectively measured accelerometer-derived activity to model motor stability (sway, jerkiness, stability)(iii) to work with industry-partner(Nerve Tumours UK) to modify the app 'Teachbrite' (https://psyc.bbk.ac.uk/teachbrite/evolutionstudy/info.php) developed by Prof Jones' team at Birkbeck College London to study motor development in a community sample of children with NF1. The student will use eye-tracking, accelerometery, neurocognitive, and behavioural measures to investigate and extend knowledge on the motor phenotype in NF1. Data from the NF1 cohort will then be compared to low risk community samples allowing us to identify early risk biomarkers that may be associated with poor motor development at 3 years. Such markers will then be used to predict risk for motor difficulties, for clinical stratification and to define intervention targets in treatment trials. The doctoral project will be embedded within two larger studies (i) a larger MRC programme Grant (Jones) investigating infancy neurocognitive development (ii) the EDEN (Early Development in Neurofibromatosis. Training will be provided in developmental, experimental and behavioural assessments. The student will spend 12 weeks at the world renowned Birkbeck babylab, London under the supervision of Jones and Begum Ali, where they will be trained in the collection of eye tracking and accelerometery in infants and toddlers. The student will benefit from clinical links and expertise in child neurodevelopment and strong links to clinical genetics expertise in Manchester.