Molecular genetic and morphologic integration in malformations of the nervous system for etiologic classification

Molecular genetics has brought new insight into the etiology and pathogenesis of nervous system malformations, and provided a means of precise genetic diagnosis including the prenatal detection of many cerebral dysgeneses. Many cerebral malformations previously thought to be a single disorder are now known to be common end results of many independent genetic mutations. Examples are holoprosencephaly and lissencephaly. Gradients of genetic expression along the axes of the neural tube established at the time of gastrulation may explain many varieties and clinical expressions of cerebral malformations, including the involvement of non-neural tissues, such as midfacial hypoplasia from defective neural crest migration. A new classification of CNS malformations is proposed that integrates, but does not discard traditional morphologic criteria, but integrates them with new molecular genetic criteria.