Genomic copy number variation in disorders of cognitive development.

OBJECTIVE: To highlight recent discoveries in the area of genomic copy number variation in neuropsychiatric disorders including intellectual disability, autism, and schizophrenia. To emphasize new principles emerging from this area, involving the genetic architecture of disease, pathophysiology, and diagnosis.
METHOD: Review of studies published in PubMed including classic studies of genomic disorders and microarray and copy number studies in normal controls, intellectual disability, autism, and schizophrenia.
RESULTS: The advent of novel microarray technology has led to a revolution in the discovery of classic and novel copy number variants (CNVs) in various disorders affecting cognitive development. Across autism and schizophrenia, global CNV burden and de novo CNV burden are associated with disease. Also, specific recurrent CNVs may be associated with several DSM conditions. Each condition is also associated with heterogeneous and individually rare CNVs.
CONCLUSIONS: CNVs play an important role in the genetic architecture of the childhood neuropsychiatric disorders discussed. This discovery appears to suggest an important role for the strict regulation of gene dosage in the neurodevelopmental roots of these conditions. Microarrays have emerged as high-yield tests in the diagnosis and molecular subtyping of the childhood-onset disorders involving cognitive development. In summary, CNV studies in disorders of cognitive development have revealed interesting and important new insights and have opened an avenue of investigation that holds great promise for neuropsychiatric disease.