MULTIPLE SITES OF ANTERIOR NEURAL-TUBE CLOSURE IN HUMANS - EVIDENCE FROM ANTERIOR NEURAL-TUBE DEFECTS (ANENCEPHALY)

Objective. Anterior neural tube closure in humans is thought to occur via a continuous process, culminating in the closure of the anterior n europore. Recent studies have demonstrated that, in some species, the process is discontinuous, with four separate sites of closure initiati on. In this study, we tested the hypothesis that humans, like mice and other experimental animals, have multiple sites of anterior neural tu be closure. Methods. Twenty human fetuses and neonates with open anter ior neural tube defects were identified. The rostral and caudal bounda ries of each defect was localized on a model cranium upon which was su perimposed the four sites of anterior closure characterized in the mou se. Results. Of the 20 cases, 7 (35%) defects involved the frontal reg ion, 7 (35%) were limited to the parietal region, 4 (20%) to the occip ital region, and 2 (10%) involved both the parietal and occipital regi ons. These defects clustered into discrete regions, corresponding to s ites of closure in the mouse model. The location of the defects fell i nto two categories; those occurring at the junction of two closures, a nd those occurring within a single closure. Conclusion. The results of this study support the hypothesis that humans, like other species, ha ve multiple sites of anterior neural tube closure. Furthermore, the da ta provide evidence for two mechanisms leading to anterior neural tube defects: one resulting from the failure of a closure to occur, and th e second from the failure of two closures to meet. The findings provid e insight into the variations observed in the location, recurrence ris k, and etiologies of anterior neural tube defects in the human populat ion.