Schizophrenia and 22q11.2 Deletion Syndrome

Abstract 22q11.2 deletion syndrome (22q11.2DS), also known as velocardiofacial syndrome, is the most frequent known interstitial deletion found in humans. It is associated with high rates of psychiatric disorder and, in particular, schizophrenia (approximately 30%) and schizophrenia‐spectrum disorders. The 22q11.2 region is rich in genes coding for brain development, and consequently, deletion of 22q11.2 provides a useful neurodevelopmental model for understanding the evolution of psychotic disorders in both 22q11.2DS and the nondeleted general population. 22q11.2DS is also associated with significant structural and functional neuroanatomical abnormalities, which underlie the high rates of psychosis seen in affected individuals. Further research is currently underway to determine the cognitive, genetic and neuroanatomical correlates of psychosis seen in the disorder. Key Concepts: 22q11.2DS provides for a genetic and neurodevelopmental model for understanding psychotic disorder seen not only with the syndrome but can also be extrapolated to the general nondeleted population. Although 22q11.2DS is associated with marked phenotypic variability, psychiatric disorder and, in particular, schizophrenia‐spectrum disorders occur in approximately 30% of deleted individuals. Schizophrenia‐spectrum disorders arise as prodromal or subthreshold psychotic symptoms during childhood and adolescence followed by subsequent expression during adulthood where it is largely indistinguishable from the psychosis seen in the nondeleted population. Apart from being the monozygotic co‐twin of a proband with psychosis or being the offspring of parents with schizophrenia, 22q11.2 deletion is the highest known risk factor for the development of schizophrenia.