{
  "abstract": "Background 22q11.2 deletion syndrome (22q11.2DS) is the commonest chromosomal microdeletion disorder, and has previously been associated with a diverse range of neuropsychiatric and neurological manifestations. Whilst prior studies have highlighted its clinical complexity, these have often relied on smaller, highly select cohorts, limiting the generalisability of findings. Leveraging population-scale data, we provide the most comprehensive assessment of neuropsychiatric outcomes in 22q11.2DS to date, stratified by age and compared to controls matched on age, sex, and ethnicity.Methods We analysed 7,105 children and 5,902 adults with 22q11.2DS, alongside matched controls from the TriNetX database. Prevalence rates and odds ratios (ORs) were calculated for neurodevelopmental, psychiatric, and neurological conditions. Prescribing patterns and comorbidities were also assessed.Results In children, neurodevelopmental disorders were common. Intellectual disability (OR: 22.11), developmental motor (OR: 4.5) and language disorders (OR: 4.1) were highly prevalent. Autism (OR: 3.5), and ADHD (OR: 1.7) were also diagnosed at significantly elevated rates compared to controls. Notably, children with 22q11.2 DS demonstrated an elevated burden of multisystem medical comorbidities, posing additional challenges for both therapeutic interventions and multidisciplinary care. In adults, neuropsychiatric and neurological conditions spanned multiple diagnostic categories. Psychotic (OR: 8.4) and seizure disorders (OR: 7.4) showed the strongest association. Our large sample size also enabled us to demonstrate significant enrichment for functional neurological disorder (OR: 5.1), OCD (OR: 3.2), and catatonia (OR: 2.8) in cases vs controls. Sleep (OR: 2.3), anxiety (OR: 1.4), bipolar (OR: 1.9), and mood disorders (OR: 1.2) were also all significantly elevated. Individuals with psychosis in 22q11.2DS exhibited unique patterns compared to those with idiopathic psychosis. Those with 22q11.2DS were more likely to be female, white and younger at the age of index diagnosis (all p< 0.001). Prescription of psychotropics, including clozapine (OR: 2.7), were also more common in 22q11.2DS related psychosis,, as were extrapyramidal and movement disorders (OR: 4.5), underscoring the distinct prescribing challenges in this group.Conclusion This study, characterising the largest cohort of individuals with 22q11.2DS to date, underscores the profound and evolving neuropsychiatric burden of the condition across the lifespan. Distinct risks for diverse neurodevelopmental disorders were demonstrated in childhood as well as severe psychiatric and neurological outcomes in adulthood. By leveraging electronic health record data, we highlight the power of population-scale datasets to advance our understanding of rare diseases, improve personalised treatment, and inform long-term multidisciplinary care.",
  "authors": [
    {
      "affiliations": [
        "Institute of Psychiatry, Psychology and Neuroscience, King’s College, London"
      ],
      "name": "Cameron J Watson"
    },
    {
      "affiliations": [
        "Institute of Psychiatry, Psychology and Neuroscience, King’s College, London"
      ],
      "name": "Maria Rogdaki"
    },
    {
      "affiliations": [
        "Institute of Psychiatry, Psychology and Neuroscience, King’s College, London"
      ],
      "name": "Mark Edwards"
    },
    {
      "affiliations": [
        "Institute of Psychiatry, Psychology and Neuroscience, King’s College, London"
      ],
      "name": "Thomas A Pollak"
    }
  ],
  "title": "The neuropsychiatry of 22q11.2 deletion syndrome: insights from across the lifespan",
  "uid": "12e457e0-c2da-53f8-9902-117497591baf"
}