6.5‐mm human embryo with a single nasal placode: Cyclopia or hypotelorism?

Abstract

A macroscopic study on the missing elements in cyclopia (a single eye or closely approximated eyes with all intergrades in a single orbit) with or without proboscis and hypotelorism was performed on 12 human fetuses and 2 human fetal skulls. In addition, microscopic investigations were carried out on the orbital contents of the cyclops with a single eye without proboscis, crown–heel length (C–HL) 37 cm, and on the 6.5-mm-crown–rump length (C–RL) human embryo with a single nasal placode localized in front of two eye cups. In the embryo and in all 14 fetal cases the midfacial region was more-or-less deficient. In the two cyclopia cases without proboscis the nasal placode(s) had not developed at all during the embryonic period. In cases with proboscis, consisting of a single tube localized above both eyes, and in the hypotelorismic specimens, there could only have been a single nasal placode during development: a situation evident in the 6.5-mm-C–RL human embryo. In this holoprosencephalic embryo the single nasal placode was undulated, as if formed from two fused nasal placodes, and flanked by the prospective areas for the lateral nasal processes. Caudally, it was bordered by the maxillary processes. In view of the position of the single placode in this embryonic face, as described above, it is most likely that this is a preliminary stage of hypotelorism. Moreover, both medial nasal processes with the internasal groove in between, i.e., the interplacodal area, were missing. In the fetal cyclopic skulls this missing area is indicated by the agenesis of, for example, the ethmoid, nasal, and lacrimal bones; the nasal septum; and two premaxillae. All specimens under study, including the microscopically investigated cyclops with a single eye, showed elements of two eye primordia. It can be concluded, therefore, that cyclopses with or without proboscis and hypotelorismic specimens have the same abnormal stages of development of the prosencephalon in relation to the eye primordia. In cyclopia cases with proboscis, the single nasal placode develops out of the range of the maxillary processes.