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Children with rare genetic disorders more likely to have developmental and mental health problems

Last updated

18/01/23

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Children with intellectual disabilities are known to be at increased risk for a range of neurodevelopmental and mental health conditions. However, it is hard to predict with any certainty what problems a child might face in the future, which makes it difficult to anticipate what support they will need.

A major study has now highlighted the additional challenges often faced by children with intellectual disabilities, including a much-increased likelihood of being diagnosed as autistic, as well as Attention Deficit Hyperactivity Disorder (ADHD) and other mental health difficulties.

With the advent of rapid whole genome sequencing, children presenting with an intellectual disability or developmental delay are recommended to have their DNA sequenced to identify the underlying genetic cause.

To capitalise on this recent NHS development, researchers at University College London, the University of Cambridge, and Cardiff University, established IMAGINE ID, a national UK cohort study, funded by the Medical Research Foundation and the Medical Research Council (part of UK Research and Innovation).

IMAGINE-ID aims to discover how genetic changes affect children and young people’s behaviour, in order to inform better care for families and children now and in the future.

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

All the participants were aged between four and 19 years. Just under three-quarters (74 per cent) had an intellectual disability caused by a duplication or deletion of sections of DNA – a so-called copy number variant (CNV). The remaining young people had a disability caused by a single ‘spelling error’ in their DNA – a change in the A, C, G or T nucleotides – referred to as a single nucleotide variant (SNV).

Compared to the English national population, children in the study were almost 30 times as likely to have been diagnosed as autistic. In the general population, 1.2 per cent of people are diagnosed with the condition compared to 36 per cent of the study participants. Similarly, 22 per cent of the study population were diagnosed with ADHD, compared to 1.6 per cent of the general population, meaning that they were more than 13 times more likely to have the condition.

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

One in ten (11 per cent) had an anxiety disorder, a 1.5 times increased risk. Rates of childhood depression were significantly lower, at just 0.4 per cent compared with 2.1% of the general population, but this may increase over the next few years as some mental health disorders do not start until later adolescence or early adult life. Almost all of the children (94 per cent) were reported to have at least one significant physical health problem, including disturbed sleep (65 per cent), motor or movement disorders (64 per cent) or seizures (30 per cent).

We hope this work helps improve the targeting of assessments and interventions to support families at the earliest opportunity. Professor David Skuse

Dr Jeanne Wolstencroft Dr Jeanne Wolstencroft

Dr Jeanne Wolstencroft from Great Ormond Street Institute of Child Health, University College London, said: “Routine genomic testing now allows parents to understand the genetic cause of intellectual disabilities in an increasing number of children but, because so many of these conditions are rare, we still lack information on the impact this has on their children’s future mental health.

“We already know that intellectual disabilities tend to be associated with an increased likelihood of neurodevelopmental conditions, as well as emotional and behavioural difficulties, but we found that where there is an identifiable genetic cause, the likelihood is amplified considerably. This suggests that these children should be provided with early assessment and help where appropriate.”

The team has also shown for the first time that children with intellectual disability caused by a genetic variant inherited from a family member, are more likely to come from a more deprived socioeconomic background. This suggests that some parents or family members with the same variant may also have unrecognised difficulties that placed them at a social and educational disadvantage. These children were more likely to be diagnosed with a neuropsychiatric condition and were also more likely to exhibit behavioural difficulties.

Professor David Skuse Professor David Skuse

Professor David Skuse from Great Ormond Street Institute of Child Health, University College London, said: “We hope this work helps improve the targeting of assessments and interventions to support families at the earliest opportunity. We’d like to see better training for health care providers about the wider use and utility of genetic testing. We have identified its potential value in terms of prioritising children with mental health needs for child mental health services, who are currently hugely limited in the UK.”

Professor Lucy Raymond from the University of Cambridge, the study’s senior author, said: “Thanks to all the families that have taken part in our research, we’ve been able to conduct the largest study to date of the impact of rare genetic variants associated with intellectual disability. What we’ve found from parents is that these children are extremely likely to develop other neurodevelopmental or mental health conditions, which can present additional challenges both to the children and their families.”

Additional research funding was provided by the NIHR Cambridge Biomedical Resource Centre and the NIHR GOSH BRC.

This news story was adapted from a University of Cambridge press release.

Paper reference

Wolstencroft, J et al. Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE - The UK National Cohort Study. Lancet Psychiatry; 4 Aug 2022; DOI: 10.1016/PIIS2215-0366(22)00207-3