Thalidomide and misoprostol: Ophthalmologic manifestations and associations both expected and unexpected

Abstract

Thalidomide is a very potent teratogen capable of causing severe systemic malformations if the fetus is exposed during the sensitive period. Although structural anomalies of the eye can occur from thalidomide exposure, the most frequent eye complication is secondary to damage to the cranial nuclei in the brain stem, resulting in aberrant neurologic connections causing a condition of abnormal ocular movement, Duane syndrome. A less frequent anomalous neurologic complication is tearing when eating (paradoxical gustolacrimal tearing or "crocodile tears") or lack of emotional tearing. The involvement of the 6th and 7th cranial nerves, often seen together in the thalidomide-affected individual, is also characteristic of Möbius syndrome/sequence. This syndrome usually occurs sporadically, but characteristic findings of this condition have also been observed in South American children who were born after an unsuccessful attempt to induce abortion with the prostaglandin drug misoprostol (Cytotec). Aberrant tearing also occurs in some individuals with Möbius syndrome. Autism spectrum disorder (ASD), an unexpected associated finding in a Swedish thalidomide study, is now also noted in Möbius studies, in patients both with and without exposure to misoprostol.