Clinical Trial: Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: Intermediate Phenotype and Genetic Mechanisms for Psychosis and Cognitive Disturbance in 22q11.2-Hemideletion Syndrome
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.
Detailed Summary: 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
Sponsor: National Institute of Mental Health (NIMH)
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Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: March 10, 2005
Date Started: March 7, 2005
Date Completion: February 2, 2010
Last Updated: January 24, 2017
Last Verified: February 2, 2010
