The pachygyria-polymicrogyria spectrum of cortical dysplasia in X-linked hydrocephalus

Neural cell adhesion molecules (CAM) play important roles in neural develop ment, neurite outgrowth, axonal guidance, fasciculation and synapse formati on. Neuropathological studies of X-linked hydrocephalus (XLH) associated wi th L1 CAM mutations emphasize marked hypoplasia of the pyramidal tract, age nesis of the corpus callosum and septum pellucidum, and a thin cerebral man tle with hypoplastic white matter but there are no detailed studies of the cerebral cortex in the literature. We report clinical, neuroimaging, and ne uropathological findings in three boys with XLH. All had severe congenital hydrocephalus with marked thinning of the cerebral mantle and severe develo pment disabilities. The brain specimens from the three boys showed both pac hygyria and polymicrogyria, hypoplasia of the medullary pyramids, hypoplasi a of the corpus callosum, small anterior commissure, hypoplasia and poorly differentiated hippocampi. A small but patent aqueduct was present in all t hree brains. Despite the extensive cerebral malformations, the cortex in al l three brains showed normal-appearing laminar cortical neuronal architectu re and absence of gliosis. In XLH, it is likely that the poor developmental outcome of spasticity, contractures and severe mental retardation results from a disturbance of neuronal connectivity, fasciculation, and synapse for mation rather than aqueductal stenosis, increased intracranial pressure, or abnormal neuroblast migration.