Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Miller-Dieker Syndrome (MDS) [Q93]

OMIM number: 247200

Dr. med. Imma Rost

Scientific Background

The leading sign of the Miller-Dieker syndrome (MDS) is lissencephaly type I (Greek lissos: smooth), a severe early embryonic developmental disorder of the cerebral cortex which leads to a reduction of the cell layers from normal 6 to 3-4, as well as to a reduction or lack in gyration (agyria or pachygyria in the MRI) of the brain surface. Agenesis or dysgenesis of the corpus callosum is frequently observed. The children show a severe developmental delay, usually with early onset seizures and feeding difficulties, which may also lead to aspiration and pneumonia. Life expectancy is reduced. Physical features include a high forehead with bitemporal hollowing, frontal bossing, microcephaly, short nose with anteverted nares, prominent upper lip with thin upper vermilion border and posteriorly rotated ears. MDS is caused by a microdeletion on the terminal end of the short arm of chromosome 17 (17p13.3). The migration disorder is caused by the deletion of the LIS1 or PAFAH1B1 gene; the complex phenotype of MDS with severe lissencephaly, additional growth disorder, facial abnormalities and occasionally additional malformations is caused by the additional deletion of at least the YWHAE gene in the sense of a contiguous gene syndrome. Approx. 80% of the deletions of MDS are de novo, approx. 20% result from a balanced chromosome rearrangement inherited from a parent.