Caudal dysgenesis in staged human embryos: Carnegie stages 16-23

The severity of expression of malformations of the median axis in the caudal region of human embryos is highly variable and ranges from caudal dysgenesis and sirenomelia to simple sacral hypoplasia. Several forms of sacral dysgenesis may be discovered later in life. This shows that caudal malformations of relatively lesser severity should occur at a greater frequency than actually reported. In the present study we looked at the morphology and histology of some human embryos with caudal dysgenesis. Several developmental alterations of the median axis were observed. These included significant reduction in the craniofacial mesenchyme characterized by hypoplasia of the pharyngeal arches, palatal shelves, and agenesis or hypoplasia of the auricular hillocks at the rostral end, absence of the caudal trunk from midsacral to all coccygeal segments, vertebral fusion or agenesis, defective development of the primary and secondary neural tubes, rectal and urinary tract dysgenesis, and deficiency, malrotation, and deficiency of the limbs at the caudal end. Hindlimb malformations included bilateral agenesis (one case), meromelia, and various forms of abnormal rotation, but no instances of sirenomelia were present. Radial dysgenesis has been reported to be associated with caudal dyplasia in the literature, however, we observed agenesis of the ulna in one and of the fibula in another embryo. There was an impressive association between limb malformations and body wall defects. The histological studies demonstrated caudal vascular deficiency and hemorrhagic lesions in the limbs of the dysplastic embryos. The data suggest that these polytopic field defects arise very early in development possibly as result of disturbances to fundamental developmental events that share common molecular and cellular mechanisms.