Extent of duplication in lower-limb malformations suggests the time of the teratogenic insult

Investigations of vertebrate limb development have suggested that a process called "specification" instructs the cells of the future limb as to which tissues they should form. This process proceeds in a wave-like manner, starting at the most proximal levels of the future limb and ending at its distal tip. Human limb specification probably occurs during the fourth and fifth weeks of development. It is proposed that human limb duplications result from errors of specification and, furthermore, that the more distal the duplication, the later the occurrence of the teratogenic event during the specification process. Therefore, among human lower limbs with duplications, one may be able to estimate the relative time of the teratogenic event by comparing the levels at which the duplications occur.