Malformations of cortical development.
BACKGROUND
Malformations of cortical development (MCD) are increasingly recognized as an important cause of epilepsy and developmental delay. MCD encompass a wide spectrum of disorders with various underlying genetic etiologies and clinical manifestations. High resolution imaging has dramatically improved our recognition of MCD.


RESULTS
This review will provide a brief overview of the stages of normal cortical development, including neuronal proliferation, neuroblast migration, and neuronal organization. Disruptions at various stages lead to characteristic MCD. Disorders of neurogenesis give rise to microcephaly (small brain) or macrocephaly (large brain). Disorders of early neuroblast migration give rise to periventricular heterotopia (neurons located along the ventricles), whereas abnormalities later in migration lead to lissencephaly (smooth brain) or subcortical band heterotopia (smooth brain with a band of heterotopic neurons under the cortex). Abnormal neuronal migration arrest give rise to over migration of neurons in cobblestone lissencephaly. Lastly, disorders of neuronal organization cause polymicrogyria (abnormally small gyri and sulci). This review will also discuss the known genetic mutations and potential mechanisms that contribute to these syndromes.


CONCLUSIONS
Identification of various gene mutations has not only given us greater insight into some of the pathophysiologic basis of MCD, but also an understanding of the processes involved in normal cortical development.
Pang
Trudy
T
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Atefy
Ramin
R
Sheen
Volney
V
D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology