Cerebral developmental disorders.
OBJECTIVE
The development of the cerebral cortex progresses through defined stages including neural proliferation, neuroblast migration and neuronal differentiation. Disruptions in each of these developmental stages can lead to characteristic cerebral cortical malformations. This review provides an overview of the known genetic causes of human cerebral developmental disorders and discusses the potential molecular mechanisms that contribute to these malformations.


RESULTS
Mutations in genes that are involved in neural proliferation give rise to microcephaly (small brain). Mutations in genes that direct the onset of neuroblast migration give rise to periventricular heterotopia (clusters of neurons along the ventricles of the brain). Mutations in genes that are required for neuroblast migration cause type I lissencephaly (smooth brain) and subcortical band heterotopia (smooth brain with a band of neurons beneath the cortex). Mutations in genes that direct migratory neurons to arrest in the cortex lead to type II lissencephaly (smooth brain with clusters of neurons along the surface of the brain).


CONCLUSIONS
The identification of causative genes involved in the formation of the cerebral cortex now allows for a rational approach with which to interpret the underlying mechanistic basis for many of these disorders.
Lian
Gewei
G
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Sheen
Volney
V
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D000293:Adolescent; D001927:Brain Diseases / Q000235:genetics* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology* / Q000254:growth & development; D002648:Child; D002675:Child, Preschool; D003285:Contractile Proteins / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics; D047109:Fetal Development / Q000502:physiology; D064448:Filamins; D006801:Humans; D007223:Infant; D008840:Microfilament Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics
D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human