X linked lissencephaly and subcortical band heterotopia (XLIS/SBH) is a disorder of cortical development, which causes classical lissencephaly with severe mental retardation and epilepsy in hemizygous males and SBH associated with milder mental retardation and epilepsy in heterozygous females.
A novel human gene, TRPC5, was cloned from the region of Xq23 that contains loci for nonsyndromic mental retardation (MRX47 and MRX35) and two genes, DCX and HPAK3, implicated in two X-linked disorders (LISX and MRX30).
In human patients, cortical dysplasia produced by Doublecortin (DCX) mutations lead to mental retardation and intractable infantile epilepsies, but the underlying mechanisms are not known.
Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy.