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

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00105274
First received: March 10, 2005
Last updated: February 3, 2010
Last verified: February 2010
  Purpose

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.

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Condition
DiGeorge Syndrome
Velocardiofacial Syndrome
22q11.2 Syndrome

Study Type: Observational
Official Title: Intermediate Phenotype and Genetic Mechanisms for Psychosis and Cognitive Disturbance in 22q11.2-Hemideletion Syndrome

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Study Start Date: March 2005
Estimated Study Completion Date: February 2010
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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

(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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00105274

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00105274     History of Changes
Other Study ID Numbers: 050110, 05-M-0110
Study First Received: March 10, 2005
Last Updated: February 3, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Velocardiofacial Syndrome
Susceptibility Genes
Neuroimaging
22q11.2
Psychosis
Mircodeletion
DiGeorge Syndrome
22q11.2 Syndrome

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

ClinicalTrials.gov processed this record on November 25, 2014