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At a glance

Polymalformative Teratogenic Syndrome characterized by short stature, skull anomalies (cranial dysostosis), limb anomalies, hydrocephalus, and facial anomalies (abnormal ear auricles, hypertelorism, micrognathia, cleft palate).


Aminopterin Antenatal Infection.


Aminopterin is a folic acid antagonist that was used both as an antineoplastic and an abortive agent in the 1950s and 1960s. It is teratogenic when absorbed during the first trimester of pregnancy (affecting the morphogenesis of 50% of embryos and fetuses). Methotrexate, which is the methyl derivative of aminopterin, can have the same effect in dosages greater than 10 mg/week. The possible association between this medical condition and in-utero methotrexate exposure has been reported.


Diagnosis is clinical based on the drug ingestion history and the dysmorphism of the fetus.

Clinical aspects

Drug ingestion causes fetal and early postnatal death, but some infants survive beyond the first year. The main feature is growth deficiency that usually has a prenatal onset and continues postnatally. They are born with microcephaly and hypoplasia of most of the cranial bones. Other facial feature findings are the presence of a broad nasal bridge, shallow supraorbital ridges, prominent eyes, low-set ears, epicanthal folds, micrognathia, and maxillary hypoplasia. Intelligence and motor development are normal. Musculoskeletal findings are a relative shortness of the limbs, mostly of the forearm, and talipes equinovarus. Other occasional abnormalities, such as cleft palate, neural tube defect, dextroposition of the heart, and hypotonia, are observed.

Precautions before anesthesia

Carefully evaluate the airway.

Anesthetic considerations

Tracheal intubation may be difficult because of the micrognathia and the maxillary hypoplasia, so have an alternate intubation tool readily available.

Pharmacological implications

Avoid long-acting muscular relaxants until the airway is secured.

Other conditions to be considered

This syndrome can be compared to other toxic antenatal expositions, such as Fetal Methotrexate Syndrome, Fetal Aminopterin-like Syndrome (exposure to antifolate drugs other than aminopterin).

  • Retinoic Acid Embryopathy: Medical condition characterized by significant anomalies in response to the teratogenic effects of retinoic acid (isotretinoin, 1,3-cis-retinoic acid [Accutane]). The risk to the fetus is usually present when maternal ingestion of Accutane occurs after day 15 of pregnancy. The patient presents with microcephaly, facial asymmetry, facial nerve palsy, micrognathia, and cleft palate. The cardiovascular system includes conotruncal anomalies. Mental retardation and hydrocephalus have been reported. There is an association with ☞DiGeorge Syndrome. Anesthetic considerations include difficult airway management, hypocalcemia (because of parathyroid gland dysfunction), and the potential for congenital heart defects.

  • ☞Fetal Retinoid Syndrome: Presents characteristic pattern of mental and physical birth defects resulting from maternal use of retinoids, the synthetic derivatives of vitamin A, ...

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