X-LINKED MALFORMATIONS OF NEURONAL MIGRATION

Malformations of neuronal migration such as lissencephaly (agyria-pach ygyria spectrum) are well-known causes of mental retardation and epile psy that are often genetic. For example, isolated lissencephaly sequen ce and Miller-Dieker syndrome are caused by deletions involving a liss encephaly gene in chromosome 17p13.3, while many other malformation sy ndromes have autosomal recessive inheritance. In this paper, we review evidence suppor ting the existence of two distinct X-linked malformat ions of neuronal migration. X-linked lissencephaly and subcortical ban d heterotopia (XLIS) presents with sporadic or familial mental retarda tion and epilepsy, The brain malformation varies from classical lissen cephaly, which is observed in males, to subcortical band heterotopia, which is observed primarily in females, The XLIS gene is located in ch romosome Xq22.3 based on the breakpoint of an X-autosomal translocatio n. Bilateral periventricular nodular heterotopia (BPNH) usually presen ts with sporadic or familial epilepsy with normal intelligence, primar ily in females, although we have evaluated two boys with BPNH and seve re mental retardation. The gene for BPNH has been mapped to chromosome Xq28 based on linkage studies in multiplex families and observation o f a subtle structural abnormality in one of the boys with BPNH and sev ere mental retardation.