Genetics of neural tube defects

Neural tube defects are a complex, heterogeneous, and multifactorial group of disorders. In humans it is estimated that 80% of neural tube defects are “multifactorial” and are influenced by both genetic and environmental factors. It appears that 70% of neural tube defects in humans are related to periconceptional deficiency of folic acid in the mother. As yet unknown genetic factors must play a role in the folic acid deficiency effect. The aim of this article was to 1) outline what is known about the genetics of neural tube defects in humans, 2) review the multiple factors (environmental and genetic) involved in the genesis of neural tube defects, 3) provide an update on the chromosomal disorders associated with neural tube defects, 4) discuss single-gene disorders and list known syndromes associated with neural tube defects covering their genetic aspects, 5) list known teratogens that may interfere with the development of the neural tube and discuss their potential genetic basis, 6) discuss multifactorial inheritance of neural tube defects and discuss recurrence risk, 7) discuss the role of nutrition in the development of neural tube defects, 8) discuss the association of twinning with neural tube defects, 9) discuss parent-of-origin effects that have been observed in association with neural tube defects, 10) discuss folate-resistant neural tube defects, 11) discuss the genetics of neural tube defects in the context of recurrence risk and reduction in recurrence risk through periconceptional maternal folic acid supplementation, and 12) discuss therapies which may be employed in the future to prevent neural tube defects. MRDD Research Reviews 1998;4:269–281. © 1998 Wiley-Liss, Inc.