Asplenia and polysplenia malformation complexes explained by abnormal embryonic body curvature

Asplenia and polysplenia malformation complexes characteristically have severe cardiovascular defects and visceral heterotaxy. We examined the hypothesis that the conditions may arise from an altered timing of development of embryonic body curvature: delayed in asplenia, accelerated in polysplenia. The morphologic features of the 25 patients with asplenia and 15 with polysplenia autopsied at The Johns Hopkins Hospital were determined. The time of appearance of various morphologic features and the evolution of body curvature was studied in 351 staged serially sectioned human embryos of The Carnegie Embryological Collection. All asplenia patients had severe atrioventricular canal malformations. Bilateral trilobed lungs were found in 12 patients. The polysplenia patients had severe interatrial septal defects in 10 patients; but ventricular septal defects in only six. Bilateral bilobed lungs were seen in five patients. Comparison of the time of appearance of anatomic structures in normal embryos with the observed malformations suggest that asplenia and polysplenia complexes originate in stages 13 to 15. The observations are consistent with the concept that the malformations in asplenia and polysplenia can be explained by minor alterations in the sequence of development of embryonic body curvature relative to organ maturation.