Background X-linked lissencephaly with abnormal genitalia (XLAG) is established as one disease entity. XLAG, showing severe neonatal seizure and developmental delay, is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located in Xp22.13. Arx-null mice for human XLAG model showed loss of tangential migration of GABAergic interneurons.

Objectives We investigated subpopulation of GABAergic interneurons in the brain of an infant with XLAG, who had a nonsense mutation of the ARX gene, compared with those of age-matched normal control, Miller-Dieker syndrome (MDS) as a type I lissencephaly, and polymicrogyria of Fukuyama type congenital muscular dystrophy (FCMD) as a type II lissencephaly.

Methods We used paraffin-embeded brain tissues of two XLAG, three MDS and four FCMD, with an informed consent of their parents. We performed immunocytochemistry for interneuron and migration markers.

Results Glutamic acid decarboxylase (GAD) and calretinin (CR) containing (+) cells were significantly very few in the neocortex and located in the white matter and neocortical subventricular zone. In the neocortical subventricular region, the GAD+ and CR+ cells had Mash^-1 protein, like a radial migration marker, and nestin protein. On the contrary, MDS showed relative low concentration of GAD+ cells. FCMD revealed random distribution of these marked cells.

Conclusions ARX controls not only tangential migration of GABAergic interneurons from the ganglionic eminence, but also may serve to induce radial migration from the neocortical subventricular zone. MDS and FCMD also demonstrated abnormal distribution of neocortical interneurons, but those severities are different in each type of lissencephaly.