Genetics and Psychopathology in the 22q11 Deletion Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00161109
Recruitment Status : Unknown
Verified October 2004 by UMC Utrecht.
Recruitment status was:  Recruiting
First Posted : September 12, 2005
Last Update Posted : October 13, 2006
Netherlands Brain Foundation
Children's Hospital of Philadelphia
Information provided by:
UMC Utrecht

Brief Summary:

The purposes of this study are to:

  1. study the nature and longitudinal course of psychiatric symptoms in children with the 22q11.2 deletion syndrome and
  2. identify genes that contribute to the occurrence of these symptoms.

Condition or disease
Chromosome 22q11.2 Deletion Syndrome

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Detailed Description:

The study of genes that are implicated in various mental diseases is increasingly relevant. The association between a gene and a disease can provide valuable information on how the neurobiology of the brain is altered, by studying the function of the protein encoded by the gene. This information is important for the development of new treatments.

However, the identification of these “disease” genes is difficult, due to the complexity of human behavior and the interaction of multiple genes. Moreover, the human genome consists of approximately 35,000 genes, further complicating the matter.

The situation is simplified when a psychiatric disorder and a genetic anomaly co-occur; assuming a causative relation, one can focus on the implicated genetic region.

The 22q11-deletion syndrome (22q11DS) is an example of this type; this syndrome is caused by a disappearance (“deletion”) of 20-30 genes in a well-defined region on chromosome 22. People with 22q11DS have a high risk of autism and psychosis, therefore one or more genes in the 22q11DS region must be associated with these disorders.

In this study we aim to identify these genes, by carefully studying psychiatric symptoms (and additional parameters of brain functioning) in a large sample of 22q11DS children and subsequently statistically correlate these findings to specific genes within the 22q11DS region. If genes associated with autism and/or psychosis in the 22q11DS population can be found, they may help to understand the underlying neurobiology that cause these diseases, not only in 22q11DS patients but in the general population as well.

The aims of this study are:

  1. STUDY NATURE AND DEVELOPMENTAL COURSE OF PSYCHIATRIC SYMPTOMS. To perform a prospective longitudinal follow up study of a sample of children with the 22q11.2 deletion syndrome with specific attention to a) possible predictors for psychosis in psychiatric and neuropsychological profile and b) a possible correlation between autistic symptoms and psychosis.
  2. ASSESS THE CORRELATION OF 22q11.2 DELETIONS WITH THE PSYCHOSIS / AUTISTIC PHENOTYPE AND ASSOCIATED ENDOPHENOTYPES: To evaluate whether the size of the deletion and / or polymorphisms at selected candidate genes within the 22q11.2 deleted region contribute to the psychosis and or autistic phenotype or to related psychophysiologic / neuropsychological impairments in 22q11DS.


With regard to aim 1:

A large sample (a final sample size of 100-120 is anticipated) of children with 22q11DS, aged 10 - 20 year, is broadly phenotyped using standard psychiatric assessment methods, intelligence and selected neuropsychological tests as well as psychophysiological assessments. Approximately 4 years after the initial assessment a follow up assessment is planned. Age and IQ matched children without the deletion (or any other apparent genetic abnormality) are used as a control group.

With regard to aim 2:

  • Phenotypes: Individuals with a certain endophenotype (“cases” e.g. the presence of autistic symptoms or a decreased Pre Pulse Inhibition or impaired performance on executive tasks) will be compared to children without that particular phenotype (“controls”).
  • Genetic analysis:

    • Genotyping consists of:

      1. assessment of the size of the deletion and
      2. genotyping single nucleotide polymorphisms (SNPs) across the deleted genomic region. Genotyping will be performed using approximately 75 previously characterized SNPs, with an increased density of SNPs in the target candidate genes (~3-5 SNPs per candidate gene). In order to determine whether a haplotype and/or variants of genes within region 22q11.2 contribute to the autistic phenotype and related neuro-psychological impairments in patients with the deletion, we will identify DNA polymorphisms using existing databases. We will then genotype patients with the 22q11.2 deletion for the selected polymorphisms and compare the allele frequencies and haplotype combinations in 22q11DS patients with the phenotype (“cases”) to those deleted patients without these findings (“controls”) applying chi-square, Fisher’s exact test, and other statistical genetic methods as appropriate.

Study Type : Observational
Enrollment : 175 participants
Observational Model: Defined Population
Observational Model: Natural History
Time Perspective: Longitudinal
Time Perspective: Prospective
Official Title: Genetics and Psychopathology in the 22q11 Deletion Syndrome
Study Start Date : October 2002
Study Completion Date : October 2012

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 22q11.2 deletion confirmed with fluorescence in-situ hybridization (FISH)

Exclusion Criteria:

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00161109

Contact: Jacob AS Vorstman, M.D. 215 590 3863

United States, Pennsylvania
Children's Hospital of Philadelphia, Dpt of Genetics and Dpt of Child and Adolescent Psychiatry Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jacob AS Vorstman, M.D.    215-590-2862   
UMC Utrecht, Dpt of Child and Adolescent Psychiatry Recruiting
Utrecht, Netherlands, 3508 GA
Contact: Herman van Engeland, M.D., Ph.D.    +31 30 2506362   
Sponsors and Collaborators
UMC Utrecht
Netherlands Brain Foundation
Children's Hospital of Philadelphia
Study Director: René S. Kahn, M.D., Ph.D. UMC Utrecht, The Netherlands

Additional Information: Identifier: NCT00161109     History of Changes
Other Study ID Numbers: P03.0377C
First Posted: September 12, 2005    Key Record Dates
Last Update Posted: October 13, 2006
Last Verified: October 2004

Keywords provided by UMC Utrecht:
22q11.2 deletion syndrome
Deletion size
Candidate genes
Psychiatric symptoms
Neuropsychological impairments
Psychophysiological performance

Additional relevant MeSH terms:
DiGeorge Syndrome
22q11 Deletion Syndrome
Pathologic Processes
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Lymphatic Abnormalities
Lymphatic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Parathyroid Diseases
Endocrine System Diseases