Longitudinal Psychiatric and Developmental Outcomes in 22q11.2 Deletion Syndrome: A Systematic Review

Abstract

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.

Psychosis spectrum features, neurocognition and functioning in a longitudinal study of youth with 22q11.2 deletion syndrome

“…This finding remained significant after covarying for earlier history of ADHD and anxiety. The finding that deficits in executive functions are important and related to poorer outcome is consistent with previous studies (Antshel et al, 2017;Chawner et al, 2019;Jhawar et al, 2021;Maeder et al, 2016;Weinberger et al, 2018). However, our longitudinal analysis indicated that of the three executive functions measured (i.e.…”

Intracellular Citrate/acetyl-CoA flux and endoplasmic reticulum acetylation: Connectivity is the answer

“…The association between overexpression of SLC25A1 and ASD is also observed in the mouse where it manifests with altered neuronal morphology and white matter integrity [ 30 ]. Reduced gene dosage of SLC25A1 is associated with DiGeorge syndrome (also referred to as 22q11.2 hemizygous microdeletion syndrome), which manifests with developmental delay, multi-system deficits, dysmorphism and intellectual disability resembling ASD, attention deficit hyperactivity disorder (ADHD) or even schizophrenia [ [31] , [32] , [33] ]. Loss-of-function mutations in SLC25A1 are also associated with neurodevelopmental deficits and intellectual disability, intractable seizures, severe metabolic alterations, and early death [ 34 , 35 ].…”

An examination of adaptive behavior and functional outcomes in adults with 22q11.2 deletion syndrome: A parental perspective

“…This study built upon previous research by examining factors that may moderate the relationship between adaptive behavior and its relationship to ecologically valid outcomes, including living status, employment, and educational attainments. As noted in a recent systematic review, the use of data solely derived from psychological tests has limited associations with real-world outcomes (Jhawar et al, 2021). It found that a quarter of participants engaged in employment, half had attained second-level education, and only 9.9% had obtained a thirdlevel education.…”