Möbius sequence in children exposed in utero to misoprostol: neuropathological study of three cases

Misoprostol exposure in the first trimester of pregnancy has been related to congenital malformations, particularly the Möbius sequence and terminal transverse limb defects.

Neuropathological findings of three patients with Möbius sequence related to misoprostol are reported. No previous pathological studies have shown these abnormalities to be associated with misoprostol exposure in utero. The brain stem was cut serially, from the rostral mesencephalum to the caudal aspect of the medulla, and all fragments were stained with hematoxylin-eosin and cresyl violet. Old ischemic-anoxic foci of gliosis, with necrosis and calcification, dorsally situated, were present from the pons to the medulla, involving some cranial nerve nuclei (especially the IV, VII, and XII) that were partially or completely depopulated of neural cells.

The findings suggest a circulatory mechanism to the Möbius sequence, with vascular disruption involving the territory of the subclavian artery, occurring in a critical period of embryonic life between six to eight weeks postconception. These cases add further evidence of the role of misoprostol as a teratogen.