title: Neural tube defects: recent advances, unsolved questions, and controversies.
abstract: Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders.
authors.affiliation: Neural Development Unit and Newlife Birth Defects Research Centre, UCL Institute of Child Health, London, UK. a.copp@ucl.ac.uk
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copp
authors.forename: Philip
authors.initials: P
authors.lastname: Stanier
authors.forename: Nicholas D E
authors.initials: ND
authors.lastname: Greene
mesh_terms: D000818:Animals; D016208:Databases, Factual / Q000706:statistics & numerical data; D004195:Disease Models, Animal; D005492:Folic Acid / Q000378:metabolism* / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009436:Neural Tube Defects / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000628:therapy*
chemical_list: D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)