Genes, brain development and psychiatric phenotypes in velo-cardio-facial syndrome

Doron Gothelf*, Marie Schaer, Stephan Eliez

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Velo-cardio-facial syndrome (VCFS) has been in the focus of intensive research over the last 15 years. The syndrome represents a homogeneous model for studying the effect of a decreased dosage of genes on the development of brain structure and function and, consequently, on the emergence of schizophrenia-like psychotic disorder. In this review, we describe the psychiatric phenotype of children, adolescents, and young adults with VCFS. We redefine the concept of "behavioral phenotype" and suggest that psychosis fulfills the criteria of a behavioral phenotype of the syndrome. Identifying the risk factors for the emergence of psychosis in VCFS is a major goal of several large-scale longitudinal studies that are currently underway. We review the knowledge gained so far about risk factors for psychosis in VCFS, including early neuropsychiatric symptoms, development of brain structure and function, and the effect of a reduced dosage of genes from the 22q11 deletion region. Although the brain structure in subjects with VCFS is not drastically different from typically developing controls, newer imaging modalities that measure white matter tracts, cortical thickness, and cortical gyrification are likely to identify more subtle and specific neuroanatomical substrates of the syndrome. Among the 24 genes within the deletion region, the role of catechol-O- methyltransferase (COMT) on the VCFS phenotype has been investigated in depth. The findings suggest that because of haploinsufficiency of the COMT gene individuals with VCFS are exposed to a high level of prefrontal dopamine, and this interferes with their prefrontal cognitive functioning and may contribute to their high rate of psychosis and other psychiatric disorders. The other genes and environmental factors that shape the unique neuropsychiatric phenotype of VCFS are yet to be discovered.

Original languageEnglish
Pages (from-to)59-68
Number of pages10
JournalDevelopmental Disabilities Research Reviews
Issue number1
StatePublished - 2008


  • 22q11.2 deletion syndrome
  • Brain development
  • COMT
  • Cortical shape
  • Functional MRI
  • Neuroanatomy
  • Psychiatric disorders
  • Psychosis


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