Miller-Dieker syndrome (MDS) is characterized by lissencephalyI (Greek lissos=smooth), a severe early embryonic developmental disorder of the cerebral cortex that results in a reduction of cell layers from 6 (normal) to 3-4 and decreased to absent gyration (agyria or pachygyria on MRI) of the brain surface. A bar deficiency is often found. Accordingly, the children show severe developmental delay usually with early-onset seizures and feeding difficulties which may also lead to aspiration and pneumonia. Life expectancy is reduced. External features include a high arched forehead with bitemporal retractions, microcephaly, a short nose with inverted nostrils, an arched prominent upper lip, and posteriorly rotated auricles. MDS is caused by a microdeletion at the terminal end of the short arm of chromosome 17 (17p13.3). The migration disorder is caused by deletion of the LIS1 or PAFAH1B1 gene. The complex phenotype of MDS with severe lissencephaly, additional growth retardation, facial abnormalities and occasionally additional malformations is caused by an additional deletion of at least the YWHAE gene in the sense of a contiguous gene syndrome. About 80% of the deletions in MDS are new and about 20% result from a balanced parental structural change.
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