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The recent explosion of information about molecules that influence brain development provides a basis for reevaluating the causes of a number of congenital brain malformations as well as various forms of mental retardation. Thus, some forms of hydrocephalus (a constriction of the lumen of the neural tube that eventually leads to enlarged ventricles and subsequent cortical atrophy as a result of compression) can be traced to mutations of genes on the X chromosome. Similarly, fragile X syndrome, the most common form of congenital mental retardation, is associated with triplet repeats in a subset of genes on the X chromosome.
Beyond these X-linked abnormalities, there are at least two genetic disorders that compromise the nervous system generated by single gene mutations in homeobox-like transcription factors. Aniridia, which is characterized by loss of the iris in the eye and mild mental retardation, and Wardenburg syndrome, which is characterized by craniofacial abnormalities, spina bifida and hearing loss, are caused by mutations in the Pax 6 and Pax 3 genes, respectively, both of which produce transcription factors (see Box B). Finally, developmental disorders like autism and other severe learning impairments have in some instances been linked to microdeletions or duplications of specific chromosomal regions. Although the causal links between these genes and the resulting anomalies of brain development are not yet known, such correlations provide a starting point for understanding the molecular pathogenesis of many congenital nervous system disorders.