Review ArticleMalformations of Cortical DevelopmentPang, Trudy MD; Atefy, Ramin MD; Sheen, Volney MD, PhDAuthor Information From the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. V.L.S. is a Beckman Young Investigator and a recipient of the Doris Duke Clinical Scientist Development Award. Reprints: Volney Sheen, MD, PhD, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. E-mail: [email protected]. The Neurologist: May 2008 - Volume 14 - Issue 3 - p 181-191 doi: 10.1097/NRL.0b013e31816606b9 Buy Metrics Abstract 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. Review Summary: 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. Conclusion: 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. © 2008 Lippincott Williams & Wilkins, Inc.