Normal and abnormal development of the anorectum.

A study of the development of hereditary anorectal malformations in pig embryos resulted in major corrections of all current theories concerning normal and abnormal anorectal development. The principal event in anorectal development proved to be a shift of the dorsal part of the cloaca and the adjacent gut to the body surface of the tail groove. Regression of the dorsal part of the cloacal membrane forms an essential part in this process. Agenesis of this part to the membrane blocks the normal shift of the anorectum of the body surface with anorectal malformation as the result. The subtype of anomaly appeared to depend on the size and the form of this defect. Thus, small defects resulted in stenotic, ectopic perineal, and vulvar/vestibular orifices, and larger defects led to anal and anorectal agenesis. In all cases, an ectopic anal communication ("fistula") to the skin or the urogenital system developed but this was eventually lost in some cases by epithelial regression. A basic similarity between man and pig in both the normal development of the anorectum and in the morphology of the anorectal anomalies makes it likely that the same pathogenetic principle also applies to man. Deformities of the cloacal membrane may also form the basis of other congenital malformations of cloaca-derived orifices such as hypospadia, epispadia, vesical and cloacal extrophy, double urethra, and cloacal membrane agenesis.