Published data for this review were identified by a search of Medline. The search terms used were “schizophrenia”, “psychosis”, “22q11”, and “VCFS”. We included all important studies identified that showed on association between schizophrenia and VCFS. We excluded reports not written in English and case-reports.
ReviewSchizophrenia and velo-cardio-facial syndrome
Section snippets
Do people with VCFS have increased rates of schizophrenia?
There have been few studies of psychiatric disorders in children or adults with VCFS. Moreover, many are confounded by methodological constraints, including lack of operational criteria for psychiatric diagnosis, sample heterogeneity (with children and adults included in the same sample), small sample size, and lack of control groups. Nevertheless, several common temperamental features have been described in studies of children and adolescents with VCFS, including behavioural excitation, an
Do people with schizophrenia have increased rates of VCFS?
Several studies have reported an increased prevalence of chromosome 22q11 deletions in populations of people with schizophrenia. Karayiorgou and colleagues17 reported that two of 100 randomly selected individuals with schizophrenia had a 22q11 deletion. No deletions were seen in a sample of 200 healthy controls. Also, in a study of 47 individuals with childhood-onset schizophrenia, Usiskin and colleagues18 reported that three (6%) patients had a 22q11 deletion.
A more targeted approach to
Does a susceptibility locus for schizophrenia reside on chromosome 22q11?
In view of the relatively low frequency of deletion of chromosome 22q11 compared with schizophrenia, VCFS can only account for a small proportion of risk to the development of schizophrenia in the general population. However, more common mutations or polymorphisms in genes within the VCFS region might make a more general and widespread contribution to susceptibility to schizophrenia. This hypothesis is supported by linkage studies, which provide evidence for a susceptibility locus for non-VCFS
Identification of susceptibility genes for schizophrenia
There seems to be a strong argument to support the validity of an association between schizophrenia and VCFS. If this is the case, how can such an association facilitate the identification of susceptibility genes for schizophrenia in VCFS and in the wider population?
There are at least three possible strategies that can be adopted to identify the part that deletion of individual genes might play in determining the high rates of schizophrenia in VCFS. The first approach is to attempt to correlate
Clinical implications
If we accept that the association between VCFS and schizophrenia is valid, such an observation leads to important implications for clinical practice. First, clinical geneticists will need to consider the risk of schizophrenia when patients with VCFS are referred for genetic counselling. Second, doctors will need to consider a chromosome 22q11 deletion in patients with schizophrenia who present with one or more of the following: learning disability, congenital heart disease, cleft lip or cleft
Conclusions
Individuals with VCFS have high rates of psychotic disorders, particularly schizophrenia.14, 15 Furthermore, such individuals have been identified when patients with schizophrenia have been screened for the presence of chromosome 22q11 deletions.17, 19, 20 Additionally, results of molecular genetic studies suggest that a schizophrenia susceptibility locus maps to chromosome 22q11.23, 24, 25 These data lend support to the validity of an association between schizophrenia and VCFS and suggest
Search strategy and selection criteria
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