Pathobiology and genetics of neural tube defects.
Neural tube defects (NTDs), including spina bifida and anencephaly, are common congenital malformations that occur when the neural tube fails to achieve proper closure during early embryogenesis. Based on epidemiological and clinical data obtained over the last few decades, it is apparent that these multifactorial defects have a significant genetic component to their etiology that interacts with specific environmental risk factors. The purpose of this review article is to synthesize the existing literature on the genetic factors contributing to NTD risk.



To date, there is evidence that closure of the mammalian neural tube initiates and fuses intermittently at four discrete locations. Disruption of this process at any of these four sites may lead to an NTD, possibly arising through closure site-specific genetic mechanisms. Candidate genes involved in neural tube closure include genes of the folate metabolic pathway, as well as those involved in folate transport.



Although extensive efforts have focused on elucidating the genetic risk factors contributing to the etiology of NTDs, the population burden for these malformations remains unknown. One group at high risk for having children with NTDs is epileptic women receiving antiepileptic medications during pregnancy. Efforts to better understand the genetic factors that may contribute to their heightened risk, as well as the pathogenesis of neural tube closure defects, are reviewed herein.
Finnell
Richard H
RH
Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston 77030-3303, USA. rfinnell@ibt.tamu.edu
Gould
Amy
A
Spiegelstein
Ofer
O
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008818:Mice, Neurologic Mutants; D009436:Neural Tube Defects / Q000139:chemically induced / Q000196:embryology / Q000235:genetics*; D010597:Pharmacogenetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000139:chemically induced / Q000196:embryology / Q000235:genetics
D000927:Anticonvulsants; D002220:Carbamazepine; D005492:Folic Acid