Is there a core neuropsychiatric phenotype in 22q11.2 deletion syndrome?

The aim is to discuss the clinical features of psychiatric illness in 22q11.2 deletion syndrome (22q11DS), and to review current evidence that a core neuropsychiatric phenotype could underlie the full spectrum of different presentations.

Individuals carrying the 22q11.2 microdeletion are at risk for diverse psychiatric diagnoses across the lifespan, including schizophrenia in a significant minority, and anxiety or mood disorder in the majority. Symptoms and cognitive disruptions can be grouped into domains: attention-executive deficits, social-cognitive deficits, anxiety-affective dysregulation, and psychotic phenomena. These domains do not respect the boundaries of traditional diagnostic categories, and can be consistently recognized in children, adolescents and adults. There is early evidence that some symptom-domain disruptions may predict adult psychiatric morbidity.

If a core neuropsychiatric phenotype does exist in 22q11DS, its detection is likely to require dimensional assessment of subtle aspects of cognitive and emotional processing, not encompassed by current diagnostic systems. A core phenotype would account for disruptions across multiple symptom domains, directly reflecting genetic and neurobiological mechanisms. Relative severity of a core phenotype would predict risk for multiple psychiatric disorders, and could, therefore, be an important target for therapeutic and preventive interventions. A core phenotype meeting these criteria has not yet been defined for 22q11DS.