Neural tube defects: recent advances, unsolved questions, and controversies

Abstract

Neural tube defects (NTDs) are severe congenital malformations affecting around 1 in every 1000 pregnancies. Here we review recent advances and currently unsolved issues in the NTD field. An innovation in clinical management has come from the demonstration that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention by folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in UK. Genetic predisposition comprises the majority of NTD risk, 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 study of mouse NTD models shows that anencephaly, open spina bifida and craniorachischisis result from failure of primary neurulation, while skin-covered spinal dysraphism results from defective secondary neurulation. Other 'NTD' malformations, such as encephalocele, are likely to be postneurulation disorders.

Relationship between maternal blood ceruloplasmin level, catalase and myeloperoxidase activity and neural tube defects

“…Neural tube defects (NTDs) are a group of heterogeneous and complex central nervous system disorders, affecting approximately 0.5-2/1000 pregnancies [1], and contributing to significant fetal-neonatal morbidity and mortality. Most NTDs result from the primary failure of the embryonic neural tube closure during early embryogenesis.…”

DNA methylation analysis of Homeobox genes implicatesHOXB7hypomethylation as risk factor for neural tube defects

“…[1][2][3] The nature and severity of NTDs is determined by the stage and axial level at which closure fails. Cranial NTDs are mostly not compatible with life, while caudal NTDs give rise to lifelong disabilities.…”

Isolation of Human Neural Stem Cells from the Amniotic Fluid with Diagnosed Neural Tube Defects

“…Therefore, human AF-NSC banks could be established for developmental studies and preclinical testing purposes. NTDs in humans are known to be affected by complex genetic and environmental factors [18][19][20]. Fifty-one entities are associated with anencephaly alone in the Online Mendelian Inheritance in Man (OMIM) (www.ncbi.nlm.nih.gov/omim/?term = anencephaly).…”

“…In humans, the most common NTDs are anencephaly and myelomeningocele. The former results from a failed closure of the rostral end of the neural tube and is characterized by a total or partial absence of the cranial vault and cerebral hemisphere, while the latter is a defective closure of the caudal neural tube and the vertebral column [18][19][20]. Anencephaly results in the incomplete formation of the brain and skull and is therefore lethal.…”