Fetal isoretinoin syndrome

Guillermo Font, MD Mariana Solari, MD Rachell E. Koehn, MS

Definition: Fetal anomalies resulting from exposure to isoretinoin (accutane) during the first trimester or shortly before conception [1],[2],[3]

Synonyms: None

Incidence: Exposure to isotretionin in the first trimester carries a fetal malformation risk of  23 to 28 percent.[4],[5]

Etiology: Exposure to isotretionin (accutane) a vitamin A isomer, used for the treatment of cystic acne and other dermatologic diseases

Recurrence risk: Recurrence is possible if there is repeated exposure to isotretionin

Diagnosis: CNS (hydrocephalus, posterior fossa defects), craniofacial (microphtalmia, microtia or anotia, low-set ears, micrgnathia, microcephaly, cleft palate, hypertelorism, facial dysmorphism), cardiovascular (transposition of great vessels, tetralogy of Fallot, ventricular septal defect, atrial septal defect), spina bifida, and limb reduction [1],[2],[3]

Pathogenesis: isoretinoin is a retinoid, that  appears to inhibit cell migration from the cranial neural crest  during early embryonic development [6]

Associated anomalies: See diagnosis

Differential diagnosis: The heterogeneous etiologies for these fetal anomalies, require a complete ultrasound and chromosomal evaluation

Prognosis: Overall prognosis depends on the severity of the fetal malformation

Management: It is recommended that isoretinoin be discontinued at least one month prior to attempting pregnancy.  The frecuency of congenital anomalies does not appear to increase in patients who discontinued isoretinoin before conception. Patients with known exposure to isoretinoin should have an ultrasound evaluation for fetal anatomy and growth


[1] Dai WS, LaBraico JM, Stern RS: Epidemiology of isoretinoin exposure during pregnancy. J Am Acad Dermatol 26:599-606, 1992

[2] Lynberg MC, Khoury MJ, Lammer EJ, et al.: Sensitivity, specificity and positive predictive value of multiple malformations in isoretinoin embryopathy surveillance. Teratology 42:513-519, 1990

[3]  Dai WS, Hsu M-A, Itri LM. Safety of pregnancy after discontinuation of isotretinoin. Arch Dermatol 1989;125:363-5

[4]  Lammer EJ, Hayes AM, Schunior A,  Holmes LB. Risk for major malformations among human fetuses exposed to isoretinoin (13-cis-retinoic acid). Teratology 1987;35:68

[5]  Chen D, Jacobson MM, Kuntzman RG: Experience with retinoids in human pregnancy. In: Volans GN (ed). Basic Science in Toxicology. London: Francis Taylor Publi Co., 1990 Pp 473-482

[6]   Webster WS, Johnston MC, Lammer EJ, Sulik KK. isoretinoin embryopathy and the cranial neural crest: an in vivo and in vitro study. J Craniofac Genet Dev Biol 1986;6:211-22

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