misoprostol and Eye-Abnormalities

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.

Topics: Abnormalities, Drug-Induced; Adult; Autistic Disorder; Child; Child, Preschool; Cranial Nerves; Embryonic Development; Eye Abnormalities; Female; Humans; Infant; Lacrimal Apparatus Diseases; Misoprostol; Mobius Syndrome; Pregnancy; Teratogens; Thalidomide

To review the association of autism spectrum disorder (ASD) in individuals manifesting thalidomide embryopathy and Möbius sequence and compare them with three new studies in which ASD was also associated with ocular and systemic malformations: (1) a Swedish study of individuals with CHARGE association (Coloboma, Heart, choanal Atresia, developmental or growth Retardation, Genital anomaly, and Ear involvement); (2) a Swedish study of Goldenhar syndrome; and (3) Brazilian Möbius syndrome (sequence) study.. In the Swedish CHARGE study, 31 patients met the inclusion criteria (3+ or 4 of the common characteristics of the CHARGE syndrome). The same team of investigators also evaluated 20 Swedish patients with Goldenhar syndrome. In the Brazilian Möbius study, 28 children with a diagnosis of Möbius sequence were studied; some children had a history of exposure during their mother's pregnancy to the abortifacient drug misoprostol in an unsuccessful abortion attempt.. In the CHARGE study, five patients had the more severe autism disorder and five had autistic-like condition. In the Goldenhar study, two had autism disorder and one had autistic-like condition. In the Brazilian Möbius study, the systemic findings of the misoprostol-exposed and misoprostol-unexposed patients were almost undistinguishable, and ASD was present in both groups (autism disorder in five and autistic-like condition in three).. Autism spectrum disorder has been reported in two conditions with known early pregnancy exposure to the teratogenic agents thalidomide and misoprostol. In the Brazilian Möbius study, autism also occurred in both the misoprostol-exposed and misoprostol-unexposed groups. Autism also was present in patients with both CHARGE association and Goldenhar syndrome.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adolescent; Autistic Disorder; Child; Child, Preschool; Eye Abnormalities; Female; Goldenhar Syndrome; Humans; Male; Misoprostol; Mobius Syndrome; Severity of Illness Index; Teratogens; Thalidomide