Considering this discontinuous process of neurulation, it can be understood why NTDs are such a complex group of heterogeneous birth defects, with various phenotypic presentations. Failure of closure 1 leads to craniorachischisis (Figure 2(b)); failure of closures 2 and/or 3 causes exencephaly and/or anencephaly, respectively (Figure 2(c)), while failure of neurulation to progress from the site of closure 1 caudally along the spinal axis leads to spina bifida aperta (Figure 2(d)).