New trends in neuronal migration disorders

Abstract

Neuronal migration disorders are an heterogeneous group of disorders of nervous system development and they are considered to be one of the most significant causes of neurological and developmental disabilities and epileptic seizures in childhood. In the last ten years, molecular biologic and genetic investigations have widely increased our knowledge about the regulation of neuronal migration during development. One of the most frequent disorders is lissencephaly. It is characterized by a paucity of normal gyri and sulci resulting in a "smooth brain". There are two pathologic subtypes: classical and cobblestone. Classical lissencephaly is caused by an arrest of neuronal migration whereas cobblestone lissencephaly caused by overmigration. Heterotopia is another important neuronal migration disorder. It is characterized by a cluster of disorganized neurons in abnormal locations and it is divided into three main groups: periventricular nodular heterotopia, subcortical heterotopia and marginal glioneural heterotopia. Polymicrogyria develops at the final stages of neuronal migration, in the earliest phases of cortical organization; bilateral frontoparietal form is characterized by bilateral, symmetric polymicrogyria in the frontoparietal regions. Bilateral perisylvian polymicrogyria causes a clinical syndrome which manifests itself in the form of mild mental retardation, epilepsy and pseudobulbar palsy. Schizencephaly is another important neuronal migration disorder whose clinical characteristics are extremely variable. This review reports the main clinical and pathophysiological aspects of these disorders paying particular attention to the recent advances in molecular genetics.