ABSTRACT
Malformations of cortical development (MCD) are characterized by disruption of the normal cytoarchitecture of the cerebral cortex and altered cellular morphologies (for review see Walsh, 1999; Andermann, 2000; Crino, Miyata, & Vinters, 2002). MCD can affect broad regions of the cerebral cortex as in lissencephaly and hemimegalencephaly, or may be restricted to focal areas such as tubers in the tuberous sclerosis complex (TSC) or focal cortical dysplasia (FCD) with balloon cells. In lissencephaly and polymicrogyria, the normal six-layered organization of the cerebral cortex is replaced by a more primitive four-layered arrangement (Leventer, Mills, & Dobyns, 2000), whereas in FCD or tubers of TSC, there is a virtual loss of all lamination. Large collections of heterotopic neurons are identified in subcortical band heterotopia and periventricular nodular heterotopia. The morphology of individual neurons in many MCD subtypes is abnormal, suggesting a pervasive disruption of steps necessary for intact cortical development (Ferrer et al., 1992). Recent studies have identified gene mutations responsible for select MCDs. However, the developmental pathogenesis of most MCD has not been defined. As a result of defining how gene mutations lead to abnormal cortical development, a recent scheme classifies MCD according to distinct neurodevelopmental stages including cell proliferation, migration, and cortical laminar organization (Barchovich & Kuziecky, 2000).
