IMAGINE-2: Stratifying Genomic Causes of Intellectual Disability by Mental Health Outcomes in Childhood and Adolescence

In England, there are over a million people with learning disabilities, a quarter of whom are children of school age. Most moderate to severe intellectual disability (ID) has a genetic cause. In order to identify those genetic risks, the NHS is now routinely screening the DNA of children who have significant developmental delays. Being informed that their child's ID is caused by a genetic change is of value to parents. But, at present, we can rarely use that information to advise on best management of behavioural and educational issues, or to reduce the risk of poor mental health outcomes. Our study aims to fill that gap in knowledge. Our IMAGINE-ID programme of research began in 2014. By 2019 we had recruited nearly 3500 UK families whose child has ID due to a genetic cause. Using a combination of online interviews, questionnaires, and face-to-face meetings with families, we built up a comprehensive picture of those children's strengths and weaknesses. We discovered there was a far greater risk of severe behavioural and emotional problems than was previously recognised. Whilst children with ID from the general population are about six times as likely to have problems of this nature, the risk is over thirty times greater if the disability has a genetic cause. We also discovered that children whose genetic risk was inherited had more severe emotional and behavioural problems than those in which the equivalent change occurred by chance. Perhaps parents who carry the genetic anomaly could be mildly affected by it, although they do not share the same degree of disability as their child? They are more likely than other families participating in our research programme to live in disadvantaged circumstances with overcrowding, poor quality housing, and unemployment. Adverse social circumstances would contribute to parenting difficulties and exacerbate their child's problems. We need to learn more about these important points of vulnerability. Families at risk could be identified sooner, and supported more effectively in future, if we understood more about the processes that led to their difficulties. These questions will be addressed by our new research. We will follow up and interview all participants 5 years after our initial assessment, to ask: first, have the mental health issues we uncovered in the previous study persisted? Second, if they have persisted, or improved, what are the medical, educational and environmental factors that have changed since we first met those families? Most children we saw in the first study were between 6 and 13 years of age. During our follow-up, many will be entering adolescence or early adulthood. That is a time when the risks of some mental health problems become substantially greater. We will be endeavouring to discover whether the young person's behavioural and emotional adjustment, or their risk of emerging mental health disorders, is influenced by the educational, medical or other support their families have received over the past 5 years. We will be looking for clues that pinpoint those children with the best and worst outcomes. More than one in three children in IMAGINE-ID had an Autism Spectrum Disorder. A quarter had ADHD, and a similar proportion had either severe anxiety or serious challenging behaviour. What was the impact on those children's educational progress? To what extent were those conditions recognised and treated by their local medical and mental health services? To gather that information, we will supplement what we learn from parents in the course of our follow-up interviews with nationally collected records on the children's education (from the National Pupil Database) and on their medical history (from the NHS Hospital Episode Statistics Database). We will also use information from medical records to learn more about the strong association between ID with a genetic cause and seizures, which affect up to 70% of children in the IMAGINE-ID cohort