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Inherited Intellectual Disability in Children Increases Neuropsychiatric Risk

The study covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Children with intellectual disability with a genetic origin have an enhanced risk for developing neuropsychiatric disorders if the variant is familial inherited and the family is socioeconomically deprived.

Why This Matters

  • Children with developmental delay associated with a genetic variant are at increased risk for emotional and behavioral problems. Early identification of these children can lead to early assessment and treatment.

  • Socioeconomic deprivation can also impact neuropsychiatric risk in these children.

Study Design

  • Data from 3407 participants recruited to the study by referral from United Kingdom regional genetic centers (94.4%) or self-referral/patient support groups (5.6%) were collected between October 2014 and June 2019. A subset of 2770 children aged 4-19 years was identified for inclusion in this study.

  • Primary caregivers filled out the Development and Well-Being Assessment (DAWBA) online to determine the child’s physical and mental health along with educational progress. The Adaptive Behaviour Assessment System 3 was used to measure daily living skills.

  • Family members or National Health Service medical records were the source of diagnostic genomic reports. If more than one genetic variant was found, the analysis was performed using the most pathogenic variant. Postal codes were used to identify socioeconomic deprivation.

Key Results

  • Delayed developmental milestones were common in the children in this study. Language skills were delayed in 72.4% of the children, and the average age for unsupported first walking was 23 months. A special educational needs or educational healthcare plan was in place for 76.4% of the children, and 76.6% of the caregivers received a disability living allowance.

  • Neuropsychiatric disorders with clinical significance were found in 53.1% of children who had a completed DAWBA (relative risk, 4.1; 95% CI, 3.9 – 4.5; P < .0001). Autistic spectrum disorder (ASD) was identified in 35.5%, attention deficit hyperactivity disorder in 21.6%, oppositional defiant disorders in 12.1%, and anxiety disorders in 10.6%.

  • Two or more co-occurring disorders were found in 41.6%, most frequently ASD and ADHD (21.3%). Seizure disorder was found in 29.7% of the children along with disturbed sleep in 64.6%, movement or motor disorders in 63.7%, and fine motor control problems in 46%.

  • Children with a familial variant were more likely to be in a socioeconomically disadvantaged household and were at higher risk for a mental health diagnosis and behavioral difficulties, while children with a de novo variant were more likely to live in a less deprived household.


  • The participants were recruited primarily through referrals from National Health Service regional genetic centers, and it is unknown how many families declined to participate in the study.

  • Genetic variant inheritability was only identifiable in 64% of the children.

  • Parental assessment of mental health and behavior may have introduced bias into the study, although multiple assessment tools were used during the study.


  • This study was supported by the UK Medical Research Council and Medical Research Foundation.

This is a summary of a preprint research study, “Neuropsychiatric Risk in Children With Intellectual Disability of Genetic Origin: IMAGINE – The UK National Cohort Study,” written by Jeanne Wolstencroft, PhD, from NIHR Great Ormond Street Institute of Child Health, University College London, United Kingdom, and colleagues on SSRN, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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