Differences in the gyral pattern distinguish chromosome 17-linked and X-linked lissencephaly

Background: Classical lissencephaly or "smooth brain" is a human brain malf ormation that consists of diffuse agyria and pachygyria. Two genes associat ed with classical lissencephaly have recently been cloned-LIS1 from chromos ome 17p13.3 and XLIS (also called DCX) from Xq22.3-q23. Objective: We perfo rmed genotype-phenotype analysis in children with lissencephaly associated with mutations of different genes. Methods: We compared the phenotype, espe cially brain imaging studies, in a series of 48 children with lissencephaly , including 12 with Miller-Dieker syndrome (MDS), which is associated with large deletions of LIS1 and other genes in the region, 24: with isolated li ssencephaly sequence caused by smaller LIS1 deletions or mutations, and 12 with isolated lissencephaly sequence caused by XLIS mutations. Results: We found consistent differences in the gyral patterns, with the malformation m ore severe posteriorly in individuals with LIS1 mutations and more severe a nteriorly in individuals with XLIS mutations, Thus, mutations of LIS1 are a ssociated with a posterior-to-anterior gradient of lissencephaly, whereas m utations of XLIS are associated with an anterior-to-posterior gradient. We also confirmed differences in severity between MDS and ILS17, Hypoplasia of the cerebellar vermis proved to be more common with XLIS mutations, Conclu sion: It is often possible to predict the gene mutation from careful review of brain imaging studies.