Abstract Lissencephaly with cerebellar hypoplasia (LCH) is characterized by abnormal development of both the cerebral cortex and cerebellum. LCH is distinguished from classical lissencephaly (Chapter 150) by profound cerebellar hypoplasia and less severe cortical malformations. The cortical malformation in LCH is described by the term “pachygria”, (thick gyri), a term that contrasts with agyria found in severe forms of lissencephaly. LCH is inherited in an autosomal recessive fashion, and is associated with profound neurological disability, including ataxia, hypotonia, mental retardation and seizures. One form of LCH is associated with mutations in the Reelin gene (RELN), the human ortholog of the murine Reln gene, which was originally discovered as mutated in the mutant reeler mouse. Using the reeler mouse model, a great deal of progress has been made in understanding the signaling mechanisms triggered by Reelin, and other members of the Reelin signaling pathway are candidate genes for additional forms of human LCH.