A developmental and genetic classification for malformations of cortical development

Abstract

Increasing recognition of malformations of cortical development and continuing improvements in imaging techniques, molecular biologic techniques, and knowledge of mechanisms of brain development have resulted in continual improvement of the understanding of these disorders. The authors propose a revised classification based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories are based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In those cases in which the precise developmental and genetic features are uncertain, classification is based on known relationships among the genetics, pathologic features, and neuroimaging features. The major change since the prior classification has been a shift to using genotype, rather than phenotype, as the basis for classifying disorders wherever the genotype-phenotype relationship is adequately understood. Other substantial changes include more detailed classification of congenital microcephalies, particularly those in which the genes have been mapped or identified, and revised classification of congenital muscular dystrophies and polymicrogyrias. Information on genetic testing is also included. This classification allows a better conceptual understanding of the disorders, and the use of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications.

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…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).…”

“…Since the first description of the neuropathologic features of FCD provided by Taylor et al in 1971 [95], different FCD classification systems have been proposed [93,94,[96][97][98]. A task force of the Diagnostic Methods Commission of the International League Against Epilepsy (ILAE) has recently generated a new consensus classification of distinct FCD subtypes based on histopathological features [6].…”

Symmetric polymicrogyria and pachygyria associated with TUBB2B gene mutations

“…Brain pathology demonstrates abnormal development or loss of neurons in middle and deep cortical layers, variably associated with an unlayered cortical structure. 1,2 Several genes have been associated with polymicrogyria, including GPR56, SRPX2, TUBB2B, TUBB3, PAX6, TBR2, KIAA1279, NHEJ1, RAB3GAP1 and TUBA8 2-4 with all but GPR56, TUBB3 and TUBB2B found in rare syndromes. Mutations in TUBB2B have been reported in four patients and in one fetus with complex brain dysgenesis with asymmetrical, anteriorly predominant polymicrogyria.…”

Band‐like intracranial calcification with simplified gyration and polymicrogyria: A distinct “pseudo‐TORCH” phenotype

“…Polymicrogyria (PMG) is a cortical malformation characterized by an excessive number of small gyri with abnormal cortical lamination. PMG may occur as an isolated focal abnormality, or as part of a more widespread disturbance of cortical genesis [Barkovich et al, 2005;Jansen and Andermann, 2005]. It is a heterogeneous disorder and can be seen in association with congenital infection [Barkovich and Lindan, 1994], but can also occur in the context of inherited disease [Jansen and Andermann, 2005].…”