Excerpt

Although our genomes have the remarkable capacity to transmit information across generations with high fidelity, there are a small number of regions flanked by seemingly innocuous repeat sequences that can misalign during replication and lead to deletions or duplication of large stretches of DNA (from several thousand to several million bases), commonly referred to as structural or copy number variation (CNV). A number of these susceptible regions, or “hot spots,” occur throughout the genome, leading to recurrent CNVs that are associated with syndromic presentations that have been recently dubbed “genomic disorders.”

One of the first genomic disorders to be linked with neuropsychiatric symptoms is the 22q11.2 deletion syndrome (22q11.2DS), initially described by DiGeorge as a congenital syndrome of immunological (thymic aplasia), endocrine (hypothyroidism), and cranio-facial abnormalities (1). However, subsequent studies have shown that the 22q11.2 deletion is associated with a broader and more diverse phenotype than was first apparent, often including mild intellectual disability, autistic features, prominent anxiety, and attention deficit symptoms.

Most striking, however, was the recognition that approximately 25% of subjects with the 22q11.2 deletion manifest a psychotic syndrome indistinguishable from schizophrenia (2). Indeed, in a recent study of more than 41,000 subjects (3), the 22q11.2 deletion was found to be one of the strongest genetic risk factors for schizophrenia (odds ratio=67.7, 95% CI=9.3–492.8), being found in approximately 0.3% of cases with schizophrenia and almost no control subjects.

SOURCE: American Journal of Psychiatry