A Developmental and Genetic Classification for Malformations of Cortical Development

Update 2012

A. James Barkovich; Renzo Guerrini; Ruben I. Kuzniecky; Graeme D. Jackson; William B. Dobyns


Brain. 2012;135(5):1348-1369. 

In This Article

Abstract and Introduction


Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported. These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development.


Malformations of cortical development have been of interest to clinicians and neuroscientists for many decades (Friede, 1989; Sarnat, 1992; Norman et al., 1995). In 1996, the term malformation of cortical development was introduced to designate a collectively common group of disorders in children with developmental delay and young people with epilepsy; a classification scheme was introduced, based upon the earliest developmental step at which the developmental process was disturbed (Barkovich et al., 1996). Updates of the classification relied more heavily on genetics, and noted that the classification likely would never be finalized because of ongoing discoveries (Barkovich et al., 2001, 2005). Since the last revision, many new syndromes have been described, and many new genes and mutations of known genes have been identified. A new classification has been proposed for focal cortical dysplasias (FCDs), and our knowledge of the molecular biology of both normal and abnormal cortical development has evolved.

This abundance of new information has largely fit well into the existing framework, but a few structural changes and the addition of new syndromes and genes were needed to remain consistent with current literature. Here we present an updated version of the classification. Many disorders listed in Appendix 1 and Supplementary Table 2 are not mentioned in the text because discussing all of them would make the article prohibitively long. The discussions, therefore, focus on those disorders that have conceptual importance whereas the tables attempt to include as many disorders as possible, recognizing that some will inevitably be missed. Hopefully, this update will prove useful for clinicians evaluating and treating affected patients, as well as for researchers investigating these important disorders.