Arrested rotation of the outflow tract may explain tetralogy of Fallot and transposition of the great arteries.

In a previous study we investigated the rapidly changing spatial relationship of the junction of the outflow tract and great arteries in normal human embryos of Carnegie stages 15 through 19. The results suggested that the malformation complexes tetralogy of Fallot and transposition of the great arteries could be accounted for as arrests in the progression of this process of rotation. To further study this question we reviewed hearts obtained at autopsy: 28 were normal, 16 had tetralogy of Fallot, and 27 had transposition of the great arteries. The angle of the aortic to pulmonary valve axis relative to the inferior surface of the heart, as viewed from apex to base, was measured from postmortem radiographs. For normal hearts the angle was 72 degrees +/- 3 SE, 48 degrees +/- 5 for tetralogy of Fallot, and 333 degrees +/- 3 for transposition of the great arteries. Although direct comparison of hearts and embryos is difficult because of the different methods of determining angles, the valve positions in normal hearts were most similar to stage 19 embryos. Likewise, hearts with tetralogy of Fallot and transposition of the great arteries resembled stages 18 and 15, respectively. The results of the two studies are consistent with the hypothesis that tetralogy of Fallot and transposition of the great arteries arise as a result of arrests in the normal rotation of the region of the junction of the outflow tract and the great arteries.