Abstract
<jats:title>Abstract</jats:title> <jats:sec> <jats:label/> <jats:p>Neural tube defects (NTDs) are malformations of the central nervous system and axial skeleton that range from the fatal to the asymptomatic. They are among the commonest birth defects and can affect the brain, as in anencephaly, or the low spine, as in spina bifida. The defects have a strong genetic element, with a role for ‘planar polarity’ genes that regulate embryo elongation and cellular enzymes that metabolise folates. Environmental risk factors include the antiepilepsy drug, valproic acid and the fungal toxin, fumonisin. Studies of mouse embryos reveal how the neural tube closes normally, and what can go wrong leading to a defect. The actin cytoskeleton is crucial, as is the balance between proliferation and differentiation of neural cells. Folic acid can reduce the risk of an NTD although it does not prevent all cases. Other supplements, including inositol, are under investigation with the aim of improving the prevention of NTDs in future.</jats:p> </jats:sec> <jats:sec> <jats:title>Key Concepts</jats:title> <jats:p> <jats:list list-type="bullet"> <jats:list-item> <jats:p>Neural tube defects (NTDs) are common, disabling congenital anomalies of the central nervous system.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Several types of NTDs occur, depending on the embryonic event that goes wrong.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Neural tube closure is the key developmental event whose disturbance leads to spina bifida and anencephaly.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Genes and environmental factors interact to cause NTDs.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Genes of folate one‐carbon metabolism, and of the planar cell polarity pathway, are known to participate in the causation of NTDs.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Many cellular events of embryonic development have been implicated in the development of NTDs.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Folic acid supplements in early pregnancy can prevent some cases of NTD.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Novel therapies are required for the primary prevention of NTDs that do not respond to folic acid.</jats:p> </jats:list-item> </jats:list> </jats:p> </jats:sec>