PEDIATRICS Vol. 95 No. 4 April 1995, pp. 506-510
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Multiple Sites of Anterior Neural Tube Closure in Humans: Evidence From Anterior Neural Tube Defects (Anencephaly)

Jeffrey A. Golden MD1 and Gerald F. Chernoff PhD2

1 Department of Pathology, Neuropathology, Brigham and Women's Hospital, Boston, MA
2 California Environmental Protection Agency, Sacramento, CA

Objective. Anterior neural tube closure in humans is thought to occur via a continuous process, culminating in the closure of the anterior neuropore. Recent studies have demonstrated that, in some species, the process is discontinuous, with four separate sites of closure initiation. In this study, we tested the hypothesis that humans, like mice and other experimental animals, have multiple sites of anterior neural tube closure.

Methods. Twenty human fetuses and neonates with open anterior neural tube defects were identified. The rostral and caudal boundaries of each defect was localized on a model cranium upon which was superimposed the four sites of anterior closure characterized in the mouse.

Results. Of the 20 cases, 7 (35%) defects involved the frontal region, 7 (35%) were limited to the parietal region, 4 (20%) to the occipital region, and 2 (10%) involved both the parietal and occipital regions. These defects clustered into discrete regions, corresponding to sites of closure in the mouse model. The location of the defects fell into two categories; those occurring at the junction of two closures, and those occurring within a single closure.

Conclusion. The results of this study support the hypothesis that humans, like other species, have multiple sites of anterior neural tube closure. Furthermore, the data provide evidence for two mechanisms leading to anterior neural tube defects: one resulting from the failure of a closure to occur, and the second from the failure of two closures to meet. The findings provide insight into the variations observed in the location, recurrence risk, and etiologies of anterior neural tube defects in the human population.

Submitted on December 28, 1993
Accepted on July 13, 1994




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