Objective: 22q11.2 deletion syndrome (22q11DS) is a common genetic deletion syndrome associated with psychiatric disorders and developmental delays. A significant amount of 22q11DS research literature is published annually; here, we focus exclusively on longitudinal data that have been published in the past 5 years regarding psychiatric disorders and/or cognitive and social development. After a review, areas for future research consideration and clinical recommendations are presented. Methods: Articles were reviewed and organized in adherence with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews. The literature search identified 852 studies, and 22 studies met inclusion criteria. Results: Longitudinal study findings indicate that developmental considerations for youth with 22q11DS should focus on the primacy and enduring nature of social and executive functioning deficits, attention-deficit/hyperactivity disorder, anxiety, and negative symptoms of psychosis. Conclusion: From the diathesis of physiological conditions and genetic variance, 22q11DS and its associated phenotype of persistent cognitive deficits, comorbid psychiatric disorders, and social impairments likely conspire to increase the risk for stress in adolescence. The diathesis-stress framework, along with chronic stress, increases psychosis risk in individuals with 22q11DS. The existing literature has a heavy focus on the impact of the deletion on individual skills and attributes, such as cognition, but lacks information on the impact of the environment. Future 22q11DS research should consider specific aspects of social functioning, including interactions with parenting styles and family communication, as well as high demands in educational settings, as possible risk factors for psychosis.

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