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.

Teratogen exposure and congenital ocular abnormalities in Brazilian patients with Möbius sequence

“…In our study, the incidence of aberrant tearing was 29% (22) . Prior investigations have reported this same symptom in patients with Möbius sequence in Northeastern Brazil and Italy in 45% and 17.9% of children, respectively (13,22) . Lagophthalmos was also found in more than one-third of the individuals with Mobius sequence who were assessed in the present study, and this was a higher percentage than the percentage described in a previous study (14.3%) (32) .…”

“…It is approved by the Food and Drug Administration for use to prevent and treat gastroduodenal ulcers that are induced by nonsteroidal anti-inflammatories (3,13) . The use of misoprostol as an abortifacient in countries where abortion is illegal is common because of its low cost, easy administration, quick absorption, and few side effects (7,10,28) .…”

“…Poland-Möbius sequence was defined as the association of Möbius sequence with unilateral aplasia of the pec toralis major muscle and an ipsilateral hand anomaly (18) . The patients (13) underwent a multidisciplinary assessment that consis ted of clinical, ophthalmological, neurological, genetic, psychia tric, psychological, and dental examinations. In the present study, we describe the mothers' sociodemographic data and the patients' congenital ocular malformations (strabismus, lagophthalmos, aberrant tearing, and lack of emotional tearing).…”

“…Möbius sequence is a rare congenital disorder with an estimated prevalence in the general population of 1:500 to 1:5,000 newborns (7,12) . Although most cases are sporadic and some have been re- lated to genetic mutations (13)(14)(15) , intrauterine exposure to misoprostol and other teratogens has been associated with its occurrence (16)(17)(18)(19)(20)(21) . The aim of the present study was to report the sociodemographic profiles, teratogen exposures, and congenital abnormalities in patients with Möbius sequence.…”

“…In addition, in more than 50% of cases, the environmental agent that caused a fetal anomaly is not identified (3) . Misoprostol, alcohol, cigarettes, marijuana, cocaine, and rubella have been associated with Möbius sequence (7,10,13,(16)(17)(18)20,21,29,30) . In the present study, teratogens could be identified in most cases (56%), and 9.8% of the mothers were exposed to more than one teratogen.…”