Cognitive phenotype of velocardiofacial syndrome: a review

Res Dev Disabil. 2011 Nov-Dec;32(6):2206-13. doi: 10.1016/j.ridd.2011.05.039. Epub 2011 Jul 20.


The behavioural phenotype of velocardiofacial syndrome (VCFS), one of the most common human multiple anomaly syndromes, includes developmental disabilities, frequently including intellectual disability (ID) and high risk of diagnosis of psychotic disorders including schizophrenia. VCFS may offer a model of the relationship between ID and risk of major mental health difficulties. This paper reviews literature on the cognitive phenotype and its relationship with a polymorphism of the gene coding for catechol O-methyltransferase (COMT), a gene haploinsufficient in VCFS which modulates prefrontal dopamine levels. Principal features of the variable cognitive phenotype of VCFS in young people are ID, superiority of verbal over performance I.Q. and verbal over visuospatial memory, and difficulties with number and object magnitude comparisons, time perception and memory for serial order, and orienting of attention. Despite some improvements with age, problems with higher order attentional tasks involving planning persist, possibly modulated by COMT activity levels. Candidate cognitive endophenotypes include problems with retrieval of contextual information from memory and in executive control and focussing of attention. Longitudinal research using common core batteries of psychometric assessments, and experimental measures of cognitive function capable of direct translation for use with animal models, will further advance understanding of the developmental dynamics of VCFS.

Publication types

  • Review

MeSH terms

  • Chromosome Deletion
  • Chromosomes, Human, Pair 22
  • Cognition Disorders / genetics
  • Cognition Disorders / physiopathology
  • DiGeorge Syndrome / genetics*
  • DiGeorge Syndrome / physiopathology*
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology*
  • Phenotype