Cleft of the lip and/or palate is a common birth defect worldwide and occurs at a rate of one in 650 live births in the UK. Being born with cleft places a significant burden on children, their families and the health system as they require surgery (multiple times depending on cleft type), and other interventions to improve appearance, speech, hearing, dentition and other adverse outcomes. They are also at increased risk of psychological, psychiatric and cognitive problems [1]. There are several possible mechanisms underlying these associations that may be operating alone or together. First, they may reflect the psychological, developmental and social impacts of clefting and its treatment. Second, they may reflect genetic factors either as pleiotropic outcomes of genetic susceptibility to clefting or as independently inherited genetic risk.
The aetiology of both cleft and of psychiatric disorders is complex, with common risk alleles [3] [4] of individually small effects as well as rare genetic mutations of large effect and environmental factors playing roles. One group of rare mutations of large effect are Copy Number Variants (CNVs), referring to deletion or duplication of a part of the genome leading to differences between individuals in the number of copies of genes within the affected region. CNVs are known to increase risk of neurodevelopmental disorders (ND-CNVs), such as ADHD and autism, as well as mental health disorders but the presence and the impact of CNVs have not been studied in cleft [5].

The PhD project will provide the first detailed description of neurodevelopmental and mental health outcomes in children with cleft and examine the contributions of genetic and environmental factors. For this we will use two unique genetically informative clinical cohorts of children; the Bristol University Cleft Collective and the Cardiff University longitudinal ExperiencCes of people witH cOpy number variants (ECHO) study. Control samples will consist of the Avon Longitudinal Study of Parents and Children (ALPSAC) and the Millennium cohort which are deeply-phenotyped cohorts of typically developing children.