Current concepts of cerebral malformation syndromes

In the past, children with many brain malformations were classified as having static encephalopathies (cerebral palsy), often attributed to perinatal or prenatal distress. Understanding of the frequency and clinical manifestations of brain malformations, however, has increased dramatically in the past 10 to 15 years. During this time, it has become apparent that many static encephalopathies in children have a brain malformation as their substrate. Most of the increase in our knowledge can be attributed to advances in neuroimaging and in molecular biology. In general, radiologic analysis of the brain allows similar malformations to be classified together. Subsequent genetic analysis of the affected children often reveals the affected gene, leading to identification of the gene product and, ideally, an ultimate understanding of the molecular mechanism of malformation. Currently, many genes involved in the complicated process of neuronal proliferation, migration, and organization are being identified. Knowledge of these genes and a better radiologic classification system enable the referring physician to give better care, more sophisticated genetic counseling, and a more precise prognosis for the child. To illustrate this mechanism of classification, three groups of malformations are discussed, in which a combination of neuroimaging analysis and molecular biologic analysis have led to a new understanding of the malformation syndromes.