New Research
Psychiatric Disorders and Intellectual Functioning Throughout Development in Velocardiofacial (22q11.2 Deletion) Syndrome

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Abstract

Objective

Velocardiofacial syndrome (VCFS) is associated with cognitive deficits and high rates of schizophrenia and other neuropsychiatric disorders. We report the data from two large cohorts of individuals with VCFS from Israel and Western Europe to characterize the neuropsychiatric phenotype from childhood to adulthood in a large sample.

Method

Individuals with VCFS (n = 172) aged 5 to 54 years were evaluated with structured clinical interviews for psychiatric disorders and age-appropriate versions of the Wechsler intelligence tests.

Results

The frequency of psychiatric disorders was high and remarkably similar between samples. Psychotic disorders and depression were uncommon during childhood but increased in rates during adulthood (depressive disorders: 40.7% in young adults [aged 18–24 years]; psychotic disorders: 32.1% in adults [age >24 years]). Cognitive scores were inversely associated with age in subjects with VCFS, including patients without psychosis. Specifically, Verbal IQ (VIQ) scores negatively correlated with age, and the subjects with VCFS and psychotic disorders had significantly lower VIQ scores than nonpsychotic VCFS subjects.

Conclusions

Neuropsychiatric deficits in individuals with VCFS seem to follow a developmental pattern. The VIQ scores are negatively associated with age and rates of mood, and psychotic disorders increase dramatically during young adulthood. The data presented here support careful monitoring of psychiatric symptoms during adolescence and young adulthood in VCFS. Prospective longitudinal studies are needed to examine the nature of age-related cognitive changes and their association with psychiatric morbidity in VCFS. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(11):1060–1068.

Section snippets

Subjects

One hundred seventy-two individuals with VCFS, 90 male and 82 female subjects aged 5 to 54 years (mean age 15.9 ± 9.1 years) were evaluated at two sites, Geneva and Tel Aviv (TA). Maternal education levels were as follows: completed elementary school (24.2%), completed high school (40.6%), and completed university education (35.2%). There were no significant differences in mother's education level between Geneva and TA.

The TA sample consisted of 86 individuals with VCFS, 53 male and 33 female

Comparison of Rates of Psychiatric Disorders Between Samples

The rate of DSM-IV-TR classified psychiatric disorders present in the entire sample (73.3%) and in the TA and Geneva samples are presented in Table 1. Significantly more subjects from the TA sample were diagnosed with any type of DSM-IV-TR disorder (81.4 % versus 65.1%, p < .05), OCD (24.4% versus 7.0%, p = .001), dysthymic disorder (16.3% versus 7.0%), and ADHD (43.0% versus 25.4%, p < .05) compared with the Geneva sample. There were no significant differences between TA and Geneva samples in

Discussion

The VCFS psychiatric phenotype has been the focus of numerous research studies in recent years. Yet, to our knowledge, this is the first report using a sample of this size that covers childhood to young adulthood and reports psychiatric phenotype from two cohorts with different cultural backgrounds. The rate of most psychiatric disorders was found to be relatively comparable in the two samples, although ADHD and OCD were more prevalent in the TA sample. The large sample size also allowed for

References (51)

  • B Glaser et al.

    Language skills in children with velocardiofacial syndrome (deletion 22q11.2)

    J Pediatr

    (2002)
  • R Caplan et al.

    Thought disorder in childhood schizophrenia: replication and update of concept

    J Am Acad Child Adolesc Psychiatry

    (2000)
  • R Caplan et al.

    Formal thought disorder and psychopathology in pediatric primary generalized and complex partial epilepsy

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • JA Kirkpatrick et al.

    Congenital absence of the thymus

    Am J Roentgenol Radium Ther Nucl Med

    (1968)
  • RJ Shprintzen et al.

    A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome

    Cleft Palate J

    (1978)
  • C Carlson et al.

    Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders

    Am J Hum Genet

    (1997)
  • LD Botto et al.

    A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population

    Pediatrics

    (2003)
  • D Gothelf et al.

    Velocardiofacial manifestations and microdeletions in schizophrenic inpatients

    Am J Med Genet

    (1997)
  • AS Bassett et al.

    22q11 deletion syndrome in adults with schizophrenia

    Am J Med Genet

    (1998)
  • RJ Shprintzen

    Velo-cardio-facial syndrome: a distinctive behavioral phenotype

    Ment Retard Dev Disabil Res Rev

    (2000)
  • PD Arnold et al.

    Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders

    Am J Med Genet

    (2001)
  • KD Baker et al.

    Adolescents and young adults with 22q11 deletion syndrome: psychopathology in an at-risk group

    Br J Psychiatry

    (2005)
  • SE Fine et al.

    Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome

    J Autism Dev Disord

    (2005)
  • D Gothelf et al.

    Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome

    Am J Med Genet B Neuropsychiatr Genet

    (2004)
  • KC Murphy et al.

    High rates of schizophrenia in adults with velo-cardio-facial syndrome

    Arch Gen Psychiatry

    (1999)

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    This work was funded by the Basil O'Connor Starter Scholar Research Award of the March of Dimes (grant no. 5-FY06-590), National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award, and the National Institute for Psychobiology in Israel, founded by the Charles E. Smith family (D.G.). Data collection in Geneva was supported by a Swiss National Fund for Research to SE (PP00B-102864), as well as grants from the Eagle Foundation, the NARSAD, and the Fondation Handicap Mental & Société.

    The authors thank Lea Matasci and Catherine Pasca for the time and energy they put into organizing and sorting the Geneva data.

    This article is the subject of an editorial by Dr. Carl Feinstein in this issue.

    *

    Drs. Green and Gothelf contributed equally to this article.

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    Copyright © 2009 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.