69. THE NEUROPSYCHIATRY OF 22Q11.2 DELETION SYNDROME: AN ELECTRONIC HEALTH RECORDS STUDY.

Background 22q11.2 deletion syndrome (22q11.2DS) is the commonest chromosomal microdeletion disorder. Varied neuropsychiatric manifestations have been identified, though often in clinically ascertained cohorts. We aimed to provide real-world estimates of neuropsychiatric associations in the largest study of 22q11.2DS to date. Methods We conducted a retrospective observational study of electronic health records using TriNetX. We identified 10,831 individuals with 22q11.2DS and compared them to propensity score matched controls, deriving prevalence rates and odds ratios (ORs, 95% CIs) for neurodevelopmental, psychiatric, and neurological conditions. We further examined the clinical features of 22q11.2DS-associated autism spectrum and psychotic disorders. Results Neurodevelopmental disorders were over-represented in 22q11.2DS, including intellectual disability (OR: 33·2 [95% CI 24·4–45·2]), autism spectrum disorder (OR: 5·4 [4·6–6·2]) and developmental language disorder (OR: 6·1 [5·6–6·7]). In adults, the neuropsychiatric burden of 22q11.2DS was substantial, with schizophrenia (OR: 21·3 [11·6–39·1]), epilepsy (OR: 10·9 [8·5–14·0]) and personality disorders (OR: 3·8 [2·4–6·1]) among the strongest associations. We report novel enrichment of catatonia (OR: 18·5 [13·0–26·4]) and functional neurological disorder (OR: 2·5 [1·5–4·2]) compared to controls, and increased rates of movement disorders independent of antipsychotic use. We identified ten cases of Parkinson’s disease with an onset before the age of 50, comprising 76.9% of all cases in 22q11.2DS. Comparisons between 22q11.2DS-associated and non-22q11.2DS psychotic and autism spectrum disorders revealed differences in comorbidity and clinical outcomes. Discussion In the largest study of 22q11.2DS to date, we reveal a profound neuropsychiatric burden and demonstrate the potential of electronic health records in advancing our understanding of rare disorders.