Definition: Syndrome resulting from in utero exposure to thalidomide, characterized by fetal anomalies (limb, facial, kidney, cardiac, spinal, anal, and CNS), growth and mental function (autism) abnormalities ^{[1], [2], [3]} .

Incidence: Exposure to thalidomide in the first trimester carries a 10-50% risk of embryopathy ^{[1], [2], [3]} .

Etiology: Exposure to thalidomide in the first trimester (susceptible period is considered 34 to 50 days after the beginning of the mother's last menstrual period)^[4].

Recurrence risk: Recurrence is possible if repeated exposure during the susceptible period.

Diagnosis: Thalidomide embryopathy has been diagnosed by ultrasound examination at 17 weeks gestation^{. [5]} Limb abnormalities are characterized by phocomelia, amelia, clubfeet and supernumerary fingers. Facial abnormalities include microtia, facial palsy, orofacial cleft and microphtalmia. Cardiac malformations range from ventricular or atrial septal defect to conotruncal defects. Poor fetal growth, urogenital, gastrointestinal and spinal defects may occur^{. [1], [2]} .

Pathogenesis: Unknown, there are three hypothesis: biochemical, tissue organ, and cellular. Thalidomide may decrease expression of cell-cell adhesion receptors causing inappropriate cell-cell interaction involved in morphogenesis ^[6].

Associated anomalies: The same found under diagnosis.

Differential diagnosis: Exclusion of fetal anomalies not associated with thalidomide exposure.

Prognosis: Dependant on the severity of fetal malformation.

Management: Thalidomide is an anti-inflammatory and immunomodulant medication used to treat lupus erythematosus, rheumatoid arthritis, sarcoidosis and AIDS-related wasting disease. Recent use in the U.S. market has raised concern about exposure to pregnancy. No safe dose of thalidomide treatment during the critical period has been established. Women of childbearing age who take thalidomide would be required to use two forms of birth control and take monthly pregnancy tests. Pregnancy complicated by thalidomide exposure requires counseling for fetal malformations. Ultrasound is the only possible tool for prenatal diagnosis of thalidomide embryopathy.

References

1. Lenz W, Knapp K: Thalidomide embryopathy. Arch Environ Health 5:100-105, 1962b
2. Smithells RW, Newman CGH: Recognition of thalidomide defects. J Med Genet 29:716-723, 1992
3. Stromland K, Nordin V, Miller M, et al.:  Autism in thalidomide embryopathy: A population study. Dev  Med Child Neurol 36:351-356, 1994
4. Kajii T, Kida M, Takahashi K: The effect of thalidomide intake during 113 human pregnancies. Teratology 8:163-166, 1973
5. Gallop TR, Eigier A, Neto JG:Prenatal diagnosis of thalidomide syndrome. Prenat Diag 7:295-298, 1987
6. Tenconi R, Clementi M: Thalidomide: Teratogen and mutagen. Am  J Hum Genet 59(4 Suppl):A355, 1996