The hypothesis that during human embryogenesis there is multi-site closure of the neural tube, with possibly regionally distinct genetic control, is examined in the light of the neural tube defects (NTD) observed in trisomy 13, trisomy 18 and triploidy which survive at least to the mid-trimester. In a series of mid-trimester fetuses examined post-mortem, there were two spina bifidas in 25 cases of trisomy 13; eight spina bifidas and one anencephalic among 38 trisomy 18 individuals; and three spina bifidas in 13 triploids. Not only was there a predominance of spina bifida, but all the spina bifidas were similar in location along the neuraxis: regardless of chromosome constitution, they were all sacral or lumbosacral. A survey of the literature confirms this finding. While this regionally distinct type of NTD is not specific to a particular chromosome abnormality and thus by implication to any particular gene, it does seem to be specific to an imbalance caused by an excess of genetic material of a type which permits survival past the first few post-conception weeks, and thus lends some support to the hypothesis.