A developmental and genetic classification for malformations of cortical development: update 2012

Abstract

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.

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…1c) [28,31]. These findings support the inclusion of GNT within the group of MCD (such as FCD and TSC), characterized by cortical dysgenesis with abnormal cell proliferation ( [5]; Table 2). Mutational analysis of TSC1 and TSC2 failed to identify mutations in GGs [32], and only a somatic mutation in intron 32 of the TSC2 gene was reported in one GG patient in glial cells, but not in dysplastic neurons [33].…”

“…In 2005, Barkovich et al [93] developed a classification of MCD based on the major stages of cortical development that are possibly affected. Recently, this classification system has been revised [5] on the basis of new developments in molecular biology, genetics, and imaging features of MCD and neuropathological classifications (Table 2).…”

“…Developmental brain lesions, in particular glioneuronal tumors (GNT) and malformations of cortical development (MCD) are among the most common causes of pharmacologically intractable epilepsy (for reviews see [1][2][3][4][5]). …”

“…This integrated approach is fostered by a strong interaction between the fields of neurogenetics and basic neuroscience, and requires the implementation of new molecular diagnostic techniques in human tissue. The increasing knowledge in genetics, imaging, and pathologic features of epileptogenic developmental lesions has provided the basis for proposing new classification systems [5,6], which are used to evaluate clinical outcome and to guide more targeted studies for the identification of new antiepileptic drugs. Major advances in our understanding of the molecular pathogenesis and the pro-epileptogenic cellular mechanisms of a variety of focal developmental lesions have been made over the last decade, resulting in interesting scientific discoveries.…”

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

“…MCDs are usually highly epileptogenic, which may result from major changes in the pattern of gene expression involved in neuronal excitability 5. Focal cortical dysplasias (FCDs) are a subtype of MCD affecting >25% of all patients undergoing surgery for the treatment of refractory epilepsy 6.…”