Next-generation gene panel testing in adolescents and adults in a medical neuropsychiatric genetics clinic

Intellectual disability (ID) encompasses a clinically and genetically heterogeneous group of neurodevelopmental disorders that may present with psychiatric illness in up to 40% of cases. Despite the evidence for clinical utility of genetic panels in pediatrics, there are no published studies in adolescents/adults with ID or autism spectrum disorder (ASD). This study was approved by our institutional research ethics board. We retrospectively reviewed the medical charts of all patients evaluated between January 2017 and December 2019 in our adult neuropsychiatric genetics clinic at the McGill University Health Centre (MUHC), who had undergone a comprehensive ID/ASD gene panel. Thirty-four patients aged > 16 years, affected by ID/ASD and/or other neuropsychiatric/behavioral disorders, were identified. Pathogenic or likely pathogenic variants were identified in one-third of our cohort (32%): 8 single-nucleotide variants in 8 genes (CASK, SHANK3, IQSEC2, CHD2, ZBTB20, TREX1, SON, and TUBB2A) and 3 copy number variants (17p13.3, 16p13.12p13.11, and 9p24.3p24.1). The presence of psychiatric/behavioral disorders, regardless of the co-occurrence of ID, and, at a borderline level, the presence of ID alone were associated with positive genetic findings (p = 0.024 and p = 0.054, respectively). Moreover, seizures were associated with positive genetic results (p = 0.024). One-third of individuals presenting with psychiatric illness who met our red flags for Mendelian diseases have pathogenic or likely pathogenic variants which can be identified using a comprehensive ID/ASD gene panel (~ 2500 genes) performed on an exome backbone.