Caudal duplication syndrome: a literature review and reappraisal of its pathoembryogenesis.

Abstract

The term caudal duplication syndrome (CDS) was first introduced for complex anomalies of the distal caudal end of the trunk. The pathoembryogenesis of CDS is yet unknown, although a few theories have been proposed. We reviewed the previously proposed pathoembryogenetic theories and suggested a new perspective through the common clinical characteristics shown in CDS cases reported in the literature. We conducted a systematic literature search of the online database PubMed from October 1993 to October 2020, using the search term "caudal duplication syndrome", according to the first mention of this entity. A total of 17 articles with 23 patients were reviewed. The most common manifestations were the duplication of the distal colon, genitourinary organs, and lower spine. Specifically, the duplicated bladders or uteri contacted their counterpart through a septum, and the duplicated bowels ran parallel. More caudal structures, such as the urethra or anus, were formed separately. The duplication seems to be a result of division by an intervening septum or structure in each part. In addition, duplication was not limited to the structures formed from the caudal cell mass (CCM), such as the distal spine and spinal cord, but also included hindgut structures. Moreover, anomalies involving caudal mesenchymal defects were also present. Considering clinical manifestations that are related to all three germ layers and seemingly the overseptation of these germ layers in CDS patients, with supporting data from animal experiments, events such as late-stage errors involving Hensen's node/the primitive streak and the duplication of the CCM with the hyperplasia of the abnormally located central caudal mesenchyme are probable pathoembryogenetic mechanisms for CDS. The "leakage" of the normal growth power of the caudal mesenchyme into the intervening midline space between the two CCMs and consequent weak lateral and caudal pushes of the caudal mesenchyme may explain the association of caudal agenesis or its related anomalies with CDS. We propose a theory that by a molecular interaction, an insult causes late gastrulation phase problems, resulting in ectopic primitive streak formation, and therefore, a duplication of the CCM is induced. Subsequently, the overactivity of abnormally positioned midline mesenchyme between the two CCMs may divide the hindgut derivatives by a central septum. Underactive lateral and caudal pushes of the caudal mesenchyme may lead to an association of features shown in caudal agenesis.