Lissencephaly (smooth brain) is a severe malformation of the cerebral cortex characterized by absent or decreased convolutions. that results from arrest of neuronal migration at about 10 to 14 weeks gestation. This group of malformations includes classic lissencephaly, lissencephaly with cerebellar hypoplasia, microlissencephaly, and cobblestone lissencephaly. The first three subtypes of lissencephaly are characterized by a four-layered cortex, whereas cobblestone lissencephaly is characterized by an almost complete absence of cortical layer formation, white matter abnormalities, and enlarged ventricles, brainstem, and cerebellar, especially vermis hypoplasia.
Classic lissencephaly is quite rare and manifests with severe developmental delay, spastic quadriparesis, and severe epilepsy. The lissencephaly malformation spectrum merges with subcortical band heterotopia. The thickness of the heterotopic band and the degree of pachygyria correlate well with phenotype severity. Several different patterns of lissencephaly have been recognized, and a detailed grading system has been developed based on the severity of the gyral pattern and grading along the anterior to posterior axis.