Isotretinoin-induced craniofacial malformations in humans and hamsters.
Oral administration of 40-80 mg/d of isotretinoin (13-cis-retinoic acid, Ro 4-3780, Accutane) during the first month of human pregnancy can induce severe congenital malformation. The human Accutane dysmorphic syndrome includes rudimentary external ears, absent or imperforate auditory canals, a triangular microcephalic skull, cleft palate, depressed midface, and anomalies of the brain, jaw, and heart. Children who suffer from this syndrome have large occiputs with narrowing of the frontal bone. Microphthalmia is reported in two cases; notations are made about the orbits in three cases; and the fact that infants could not follow with their eyes is noted in three cases. A decrease in muscle tone is noted in six, cleft palate is present in four, and limb reduction defects are described in two. The cardiac malformations usually include overriding aorta, interrupted or hypoplastic aortic arch, and septation defects of atria and ventricles. There are at least two cases of abnormal origin of the subclavian arteries. Oral isotretinoin in the pregnant hamster also induces similar congenital malformations. A human case of isotretinoin-induced dysmorphia is presented and compared with other affected infants and affected hamsters. The metabolic fate and pharmacokinetic parameters of isotretinoin in humans and rodents are discussed in relation to the teratogenic response. The results suggest that humans are approximately 16 times more sensitive to the teratogenic effects of oral isotretinoin than are hamsters.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D006224:Cricetinae; D005147:Facial Bones / Q000002:abnormalities* / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D015474:Isotretinoin; D008647:Mesocricetus; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy; D012886:Skull / Q000002:abnormalities* / Q000187:drug effects / Q000648:ultrastructure; D013045:Species Specificity; D014212:Tretinoin / Q000633:toxicity
D014212:Tretinoin; D015474:Isotretinoin