Children with intellectual disabilities of genetic origin have a high risk of developing other neuropsychiatric disorders

A large-scale study of children with intellectual disabilities has revealed the additional challenges they often face, including a much higher chance of being diagnosed as autistic, as well as Attention Deficit Hyperactivity Disorder (ADHD) and other mental health problems.

With the advent of rapid whole genome sequencing, it is recommended that children with intellectual disabilities or developmental delays have their DNA sequenced to identify the underlying genetic cause.

To take advantage of this recent NHS development, researchers from the University of Cambridge, University College London and Cardiff University have launched IMAGINE ID, a national UK cohort study that aims to discover how genetic changes affect the behavior of children and young people, to provide better care. of families and children now and in the future.

Sign up The Lancet Psychiatry today the researchers published the results of an analysis of data from nearly 2,800 young people with rare genomic variants – changes in their DNA – that are associated with intellectual disability.

Thanks to all the families who participated in our research, we were able to conduct the largest study to date on the impact of rare genetic variants associated with intellectual disability. What we found from parents is that these children are very likely to develop other neurological or mental health problems, which can present additional challenges for both the children and their families.”

Lucy Raymond, Professor, University of Cambridge and senior author of the study

All participants were between 4 and 19 years old. Just under three quarters (74%) had an intellectual disability caused by duplication or deletion of pieces of DNA, a so-called copy number variant (CNV). The remaining youths had disabilities caused by a single ‘spelling error’ in their DNA – a change in the A, C, G or T nucleotides – a so-called single nucleotide variant (SNV).

Compared to the UK national population, children in the study were nearly 30 times more likely to be diagnosed as autistic. In the general population, 1.2% of people are diagnosed with the condition, compared to 36% of study participants. Similarly, 22% of the study population was diagnosed with ADHD, compared to 1.6% of the general population, meaning they were over 13 times more likely to develop the condition.

About one in eight children (12%) had been diagnosed with oppositional defiant disorder, in which children are uncooperative, defiant and hostile to others – a rate 4.4 times higher than in the general population.

One in ten (11%) had an anxiety disorder, a 1.5 times greater risk. The rate of depression in children was significantly lower, only 0.4% compared to 2.1% of the general population, but this may increase in the coming years as some mental disorders do not start until late adolescence or early adulthood. Nearly all children (94%) were reported to have at least one significant physical health problem, including disturbed sleep (65%), motor or movement disorders (64%) or seizures (30%).

dr. Jeanne Wolstencroft of the Great Ormond Street Institute of Child Health, University College London, said: “Routine genomic testing is now enabling parents to understand the genetic cause of learning disabilities in an increasing number of children, but because so many of these conditions are rare , we still have no information about the impact this will have on their children’s future mental health.

“We already know that intellectual disabilities are often associated with an increased risk of neurodevelopmental disorders, as well as emotional and behavioral problems, but we found that when there is an identifiable genetic cause, the risk is significantly increased. This suggests that these children should be provided with an early assessment and help where needed.”

The team also showed for the first time that children with intellectual disabilities, caused by a genetic variant inherited from a family member, are more likely to come from a more disadvantaged socioeconomic background. This suggests that some parents or relatives with the same variant may also have unrecognized problems that leave them social and educational behind. These children were more likely to be diagnosed with a neuropsychiatric disorder and were also more likely to have behavioral problems.

Professor David Skuse of the Great Ormond Street Institute of Child Health, University College London, said: “We hope this work will help improve the targeting of assessments and interventions to support families as quickly as possible. We would like to see better education for healthcare providers are seeing the wider use and utility of genetic testing. We have identified its potential value in terms of prioritizing children with mental health needs for pediatric mental health care, which is currently hugely limited in the UK.”

The study was funded by the Medical Research Council (part of UK Research & Innovation) and the Medical Research Foundation. Additional support was provided by the NIHR Cambridge Biomedical Resource Center and the NIHR GOSH BRC.


Reference magazine:

Wolstencroft, J., et al. (2022) Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE – The UK National Cohort Study. The Lancet Psychiatry.

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