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.

智力障碍 (ID) 包括临床和遗传上异质的一组神经发育障碍，在高达 40% 的病例中可能出现精神疾病。尽管有证据表明基因组在儿科中的临床效用，但在患有 ID 或自闭症谱系障碍 (ASD) 的青少年/成人中没有发表的研究。这项研究得到了我们机构研究伦理委员会的批准。我们回顾了 2017 年 1 月至 2019 年 12 月期间在麦吉尔大学健康中心 (MUHC) 的成人神经精神遗传学诊所评估的所有患者的病历，这些患者接受了全面的 ID/ASD 基因检测。确定了 34 名年龄 > 16 岁、受 ID/ASD 和/或其他神经精神/行为障碍影响的患者。CASK、SHANK3、IQSEC2、CHD2、ZBTB20、TREX1、SON和TUBB2A）和 3 个拷贝数变体（17p13.3、16p13.12p13.11 和 9p24.3p24.1）。无论 ID 是否同时出现，精神/行为障碍的存在，以及在临界水平上，单独 ID 的存在与阳性基因发现相关（分别为p  = 0.024 和p  = 0.054）。此外，癫痫发作与阳性基因结果相关（p = 0.024)。在出现孟德尔疾病危险信号的精神疾病患者中，三分之一具有致病性或可能的致病性变异，可以使用在外显子组骨干上进行的综合 ID/ASD 基因组（约 2500 个基因）进行鉴定。