The impact of MYT1L-syndrome on behaviour and cognition

This thesis aimed to investigate the cognitive and behavioural phenotype of MYT1L-syndrome (2p25.3 deletion), a novel cause of intellectual disability. Initially, a systematic review was conducted exploring the cognitive and behavioural phenotype of children with genetic disorders affecting chromatin remodelling, a process which the MYT1L gene is also involved in. Generally, there are clear associations between genetic disorders implicated in chromatin remodelling and neurodevelopmental conditions. Semi-structured qualitative interviews were then conducted with parents and caregivers of children with a diagnosis of MYT1L-syndrome to understand the lived experience of individuals with, and families of those, with the syndrome. Then, based on the findings of the systematic review and the insights provided by caregivers, a series of standardised measures were selected to quantitatively assess the cognitive and behavioural phenotype of individuals with the syndrome. Collectively, the findings reported within this thesis advance our understanding of the cognitive and behavioural phenotype associated with MYT1L-syndrome. The impact is often complex, and there is notably a profound impact on multiple areas of life for individuals with the syndrome. Impacted areas include reaching developmental milestones, communication and social skills, anxiety, adaptive behaviour, and sensory processing. The research also found that there is frequently a significant and multi-faceted impact on caregivers, siblings, and the wider family. Collectively, this research provides a detailed description of the cognitive and behavioural phenotype of individuals with MYT1L-syndrome. Additionally, the findings highlight some of the collective strengths and weaknesses of the cohort and recognises the intra-group heterogeneity. Clinical implications are discussed alongside recommendations for future research.