Truncus arteriosus malformation: a developmental arrest at Carnegie stage 14

The pathogenesis of truncus arteriosus malformation has been ascribed to deficiency of conotruncal ridges, failure to form a pulmonary conus, absence of the aortopulmonary septum, or hemodynamic factors. To re-examine this issue, we reviewed the morphology of 28 hearts with truncus arteriosus malformation and compared the findings to the sequences of cardiogenesis in 351 normal human embryos of the Carnegie Embryological Collection. All malformed hearts had an absent muscular outflow tract (conal) septum. The truncal valve had four commissures and/or raphes, a fused commissure, in seven cases, three in 20, and uncertain status in one. All but one heart had fibrous continuity between the anterior mitral leaflet and the truncal valve. In embryos, the outflow tract was circular and lined by a layer of cardiac jelly early in Carnegie stage 14 but acquired an elliptical configuration and four cushions, with fusion of the two larger, by stage 16. Semilunar valve leaflets form at the downstream end of the cushions. The more frequent occurrence of three rather than four commissures in the truncal valve associated with absence of a conal septum suggests that the embryonic outflow tract failed to acquire an elliptical shape and cushions that could fuse to subdivide the outflow tract and the semilunar valves anatomically. The presence of truncal valve leaflets shows that three or four cushions did form and the usual presence of mitral-truncal valve fibrous continuity supports otherwise normal outflow tract development. We conclude that a failure or delay of the circular outflow tract of early Carnegie stage 14 to acquire the elliptical configuration needed to induce formation of four cushions, two of which fuse to subdivide the outflow tract and semilunar valve primordia, is the cause of truncus arteriosus malformation.