Human neural tube defects: developmental biology, epidemiology, and genetics

Abstract

Birth defects (congenital anomalies) are the leading cause of death in babies under 1 year of age. Neural tube defects (NTD), with a birth incidence of approximately 1/1000 in American Caucasians, are the second most common type of birth defect after congenital heart defects. The most common presentations of NTD are spina bifida and anencephaly. The etiologies of NTDs are complex, with both genetic and environmental factors implicated. In this manuscript, we review the evidence for genetic etiology and for environmental influences, and we present current views on the developmental processes involved in human neural tube closure.

Figure 1

Human embryonic developmental stages during which the neural tube forms. A1&2: Carnegie stage 9 (CS9 − 20 days) the neural groove is open and anterior neural fold is visible. B1&2: CS10 (22 days). The neural folds fuses centrally leaving an open tube in the rostral and caudal region. C1, 2 & 3: CS11 (24days) The neural tube is closed except for the rostral (C2&3) and caudal neuropores. D1&2: CS12 (26 days) the caudal neuropore is closing (C2). E1&2: CS13 (28 days) The neuropores are closed. E1 corresponds to early CS13 and E2 to a late CS13. The scale bars represent 1 mm in all photographs except C3 and D2 where they represent 0.5 mm.