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The premises of this classification are (1) genetic expression in the neural tube follows gradients in the axes that are established at the time of gastrulation: vertical (dorsoventral and ventrodorsal); rostrocaudal; mediolateral. (2) Overexpression in one of these gradients generally results in duplication or hyperplasia of structures, or ectopic segmental (i.e., neuromeric) expression. (3) Underexpression in a gradient generally results in hypoplasia, noncleavage in the midline of paired structures or segmental deletion of neuromeres. These gradients may also affect the formation and migration of neural crest tissue, affecting non\u2010neural structures such as the face in the case of the mesencephalic neural crest, or induction of paraxial mesodermal in the posterior fossa. Additional criteria of the new classification allow for other genetic influences on developmental processes, such as cellular lineage, exemplified by tuberous sclerosis, and hemimegalencephaly. It is essential that the CNS be considered as a whole and classification not be regionalized, as to the cerebral cortex, because the limit of the rostrocaudal gradient may account for variability in clinical manifestations. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.20663","type":"journal-article","created":{"date-parts":[[2004,4,14]],"date-time":"2004-04-14T15:01:21Z","timestamp":1081954881000},"page":"386-392","source":"Crossref","is-referenced-by-count":58,"title":["Integrative classification of morphology and molecular genetics in central nervous system malformations"],"prefix":"10.1002","volume":"126A","author":[{"given":"Harvey B.","family":"Sarnat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Flores\u2010Sarnat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,4,14]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"2000 Lippincott Williams & Williams Philadelphia JA Barkovich Pediatric neuroimaging"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001665-200201000-00032"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1242\/dev.126.3.525","article-title":"Mash1 regulates neuronogenesis in the ventral telencephalon","volume":"126","author":"Casarosa S","year":"1999","journal-title":"Development"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.10.1565"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1542\/peds.34.2.256","article-title":"The face predicts the brain. 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