A new classification of malformations of the nervous system based on patterns of genetic expression integrated with descriptive morphogenesis is proposed by specialists in pediatric neurology, neuropathology and embryology at the University of Washington School of Medicine, Seattle, WA, now at Cedars-Sinai Medical Center, Los Angeles, CA. The authors point out the problems with classifications based exclusively on either descriptive morphogenesis or on genetics. Their new genetic based etiological classification lists 7 main categories, each with subtypes: I, II and III, involving upregulation or downregulation of organizer genes, or over- or under-expression of ventralizing or dorsalizing genes (eg duplication or agenesis of the neural tube and spinal cord); IV, disorders of rostrocaudal gradient and/or segmentation (including Chiari II malformation, and agenesis of corpus callosum); V, aberrations in cell lineages by mutation (including hemimegalencephaly, tuberous sclerosis, and gangliogliomas); VI, involving genes that mediate migrations; VII, involving genes that attract or repel axonal growth cones; and VIII, disorders of symmetry, including hemimegalencephaly and hemihyperplasia of the cerebellum. For some malformations, as in hemimegalencephaly, the malformation is listed under two categories, V and VII, recognizing there are sometimes multiple mechanisms, involving different genes and different patterns of genetic expression. Furthermore, lesions such as infarcts acquired in fetal life may disrupt radial glial fibers and result in heterotopia from disruption of nerve cell transport and incomplete migration (included in category VI). The authors appeal for semantic precision in describing developmental disorders of the nervous system. [1]

COMMENT. The authors have written extensively on this subject, and their new etiological classification of malformations of the nervous system based on genetic expression permits inclusion of recent advances in molecular genetics integrated with morphological data. In the following article involving hemispherectomy for cortical malformations and epilepsy, the outcome was correlated with the MRI findings and cerebral morphology. Future research may facilitate correlations with genetic data based on the Sarnats’ classification.