Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome

Ania M. Fiksinski*, Maude Schneider, Clodagh M. Murphy, Marco Armando, Stefano Vicari, Jaume M. Canyelles, Doron Gothelf, Stephan Eliez, Elemi J. Breetvelt, Celso Arango, Jacob A.S. Vorstman

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The purpose of this article is to provide an overview of current insights into the neurodevelopmental and psychiatric manifestations of 22q11.2 deletion syndrome (22q11DS) in children and adolescents. The pediatric neuropsychiatric expression of 22q11DS is characterized by high variability, both interindividual and intraindividual (different expressions over the lifespan). Besides varying levels of intellectual disability, the prevalence of autism spectrum disorders, attention deficit disorders, anxiety disorders, and psychotic disorders in young individuals with 22q11DS is significantly higher than in the general population, or in individuals with idiopathic intellectual disability. Possible explanations for this observed phenotypic variability will be discussed, including genetic pleiotropy, gene-environment interactions, the age-dependency of phenotypes, but also the impact of assessment and ascertainment bias as well as the limitations of our current diagnostic classification system. The implications inferred by these observations aforementioned bear direct relevance to both scientists and clinicians. Observations regarding the neuropsychiatric manifestations in individuals with 22q11DS exemplify the need for a dimensional approach to neuropsychiatric assessment, in addition to our current categorical diagnostic classification system. The potential usefulness of 22q11DS as a genetic model to study the early phases of schizophrenia as well as the phenomenon of neuropsychiatric pleiotropy observed in many CNV's will be delineated. From a clinical perspective, the importance of regular neuropsychiatric evaluations with attention to symptoms not always captured in diagnostic categories and of maintaining equilibrium between individual difficulties and competencies and environmental demands will be discussed.

Original languageEnglish
Pages (from-to)2182-2191
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Issue number10
StatePublished - Oct 2018


FundersFunder number
National Institute of Mental HealthU01MH101722
Koninklijke Nederlandse Akademie van Wetenschappen


    • 22q11DS
    • clinical implications
    • pediatric psychiatry
    • pleiotropy
    • psychiatry
    • schizophrenia


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