Chapter 26 - Neuronal migration disorders

Abstract

Malformations of brain development can arise from disruptions in any number of interconnected developmental processes including alterations in cell fate, cell proliferation, cell death, and cell migration. Disruptions in mechanisms involved primarily in neuronal cell migration cause neuronal migration disorders (NMDs), and these disorders encompass multiple syndromes characterized by aberrations in the cellular architecture of the brain including alterations in sulci and gyri in cerebral cortex and in lamination patterns of the neocortex, cerebellum, and other structures. Alterations associated with NMDs are diverse in terms of type and severity. Such disruptions range from subtle, only seen with microscopic analysis in isolated regions, to disruptions covering large regions of the brain that are easily apparent with MRI imaging. Genetic studies have now revealed many mutations in several genes that cause syndromes associated with disorders in neuronal migration. Functional studies of the products of these genes have in turn revealed proteins and pathways required for distinct cellular processes including those involved primarily in neuronal migration and those involved in processes that indirectly alter neuronal migration when altered.