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Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study

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: NCT00105274
Recruitment Status : Completed
First Posted : March 11, 2005
Last Update Posted : July 2, 2017
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

Velocardiofacial syndrome, also known as 22q11.2 syndrome or DiGeorge syndrome, has been associated with many features such as a cleft palate, heart defects, and learning, speech and feeding problems. It is caused by the absence of a number of genes on chromosome 22, but the mechanism by which this inborn abnormality causes the clinical problems is not known.

In this study by the National Institute of Mental Health and the Office of Rare Diseases, we are recruiting participants with 22q11.2 syndrome to come for a three-day stay to our main campus in Bethesda, MD, to participate in a study in which we will investigate the genetic makeup of their cells together with several studies of brain function with advanced research imaging. The goal of this study is to understand how the genes missing in 22q11.2 syndrome are related to the increased occurrence of psychiatric problems, such as psychosis, in this syndrome. Participants must be 18-50 years of age, have some high school education and not currently be taking antipsychotic medication. Travel costs to Bethesda for participants and an accompanying person will be paid, and participants are reimbursed for their time in participating in the study. A blood draw is required. All research procedures have been designated as "minimal risk" procedures.


Condition or disease
DiGeorge Syndrome Velocardiofacial Syndrome 22q11.2 Syndrome

Detailed Description:
22q11.2 (DiGeorge MIM#188400, Velocardiofacial MIM#192430) syndrome is a hemizygous microdeletion on 22q11.2 of typically 3Mb, encompassing approximately 30 genes and mediated by aberrant homologous recombination and unequal crossing-over events between intrachromosomal flanking low-copy repeats (LCRs). The incidence is 1:4000 live births. While somatic symptoms include congenital cardiovascular and craniofacial abnormalities, recurrent infections and hypocalcemia1 , the most prevalent group of symptoms are neuropsychiatric and include cognitive dysfunction with mild mental retardation, behavioral difficulties and psychosis. The syndrome is associated with a lifetime prevalence of schizophrenia-like illness (phenotypically mostly similar to sporadic schizophrenia) of approximately 25 times that of the general population making the presence of this hemideletion the strongest known risk factor for the development of schizophrenia excepting the presence of a monozygotic twin with the illness. The 22q11 region is implicated in the risk architecture of schizophrenia by several linkage studies and harbors a number of proposed susceptibility genes including genes for Catechol-O-methyltransferase (COMT), proline dehydrogenase (PRODH) and ZDHHC8. The neural basis of these pronounced neurocognitive and psychiatric abnormalities is unknown. The present work proposes to (a) study a group of exceptionally high-functioning, normal intelligence, psychosis-free individuals with 21q11.2 syndrome using a hierarchical multimodal imaging approach to define the intermediate systems level phenotype of the disease combined with deletion mapping techniques and (b) to study the functional effects of single nucleotide polymorphisms in genes in the hemideleted region that have been implicated in schizophrenia, taking advantage of the unique fact that the hemizygous deletion allows immediate construction of molecular haplotypes and of potential epistatic allelic effects. This work is expected to (a) elucidate the pathophysiology of the CNS manifestations of the 22q11.2 syndrome and yield a brain intermediate phenotype that will allow studies in small and atypical deletion individuals in an effort to define individual genes responsible for neurocognitive deficit and increased risk for psychosis, (b) facilitate the identification of functional mechanisms underlying increased risk for schizophrenia for individual susceptibility genes in the deletion and for interacting risk alleles within the deleted locus and (c) prepare the ground for a clinical protocol in which the results from (a) and (b) can be applied to a prospective study evaluating early diagnostic and interventional approaches based on genetic risk and intermediate phenotype ascertainment in this group of patients at high risk for the development of psychosis.

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Study Type : Observational
Official Title: Intermediate Phenotype and Genetic Mechanisms for Psychosis and Cognitive Disturbance in 22q11.2-Hemideletion Syndrome
Study Start Date : March 7, 2005
Study Completion Date : February 2, 2010

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Only adults between age 18 and 50 will be studied. 22q11.2 participants: 22q11.2 deletion will be confirmed by FISH. IQ (WAIS). In phase 1: IQ in the general range of the population (greater than 85) as ascertained using the 2- and 4-subset forms of the Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999). Informed consent.


(Phase 1 only) Any lifetime diagnosis of schizophrenia, schizoaffective disorder, or schizotypal disorder and/or current pychotropic medication or any neuroleptic medication in the previous year. (all phases) Chronological age greater 50 years. Contraindication of MRI scanning (ferromagnetic metal implanted in body, prostheses containing such metal, pacemaker devices). Pregnancy. Medication affecting central nervous function. Severe somatic disorders precluding travel to the clinical center or participation in imaging procedures. Hypothyroidism not compensated by medication. Neurological disorders excluding those of exclusively peripheral location.

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): NCT00105274

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Layout table for additonal information Identifier: NCT00105274    
Other Study ID Numbers: 050110
First Posted: March 11, 2005    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: February 2, 2010
Keywords provided by National Institutes of Health Clinical Center (CC):
Velocardiofacial Syndrome
Susceptibility Genes
DiGeorge Syndrome
22q11.2 Syndrome
Additional relevant MeSH terms:
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DiGeorge Syndrome
Pathologic Processes
22q11 Deletion Syndrome
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