Fetal Aminopterin Syndrome

Polymalformative teratogenic syndrome characterized by short stature, skull anomalies, hydrocephalus, and facial anomalies (abnormal 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/wk.

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

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.

Carefully evaluate the airway.

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

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

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: Syndrome 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 Aminopterin Syndrome: Characteristic pattern of mental and physical birth defects resulting from maternal use of retinoids, the synthetic derivatives of vitamin A, during pregnancy. Affects males and females equally. Exact incidence is unknown, and because many cases of fetal retinoid syndrome often go unrecognized, the disorder is underdiagnosed. The most well-known retinoid is isotretinoin (Accutane®), a drug used for treatment of severe cystic acne. The range and severity of associated abnormalities vary greatly from case to case. Characteristic features may include prenatal and postnatal growth retardation, craniofacial malformations, and central nervous system abnormalities. The cardiovascular system is generally affected with congenital defects such as tetralogy of Fallot, ventricular septal defect, and transposition of the great vessels. Some infants may develop hydrocephalus and present with posterior fossa cysts. Learning disabilities and motor developmental delays are reported. Thymus gland dysfunction has been reported, and calcium problems caused by dysfunctional parathyroid glands are known. Additional features include polysyndactyly, skeletal malformations affecting the legs and spines, and hypotonia.

DiGeorge Syndrome: Rare immunodeficiency disorder characterized by various congenital abnormalities that develop because of defects that occur during early fetal development. These defects occur in areas known as the third and fourth pharyngeal pouches, which later develop into the thymus and parathyroid glands. The symptoms vary greatly, depending upon the extent of the missing thymus and parathyroid tissue. The primary problem caused is the repeated occurrence of various infections as a result of a diminished immune system.

CHARGE Syndrome: Life-threatening, congenital syndrome of multiple abnormalities, consisting of coloboma, heart disease, choanal atresia, mental and growth retardation, genital and urinary anomalies, and ear anomalies with deafness. The prognosis worsens if the disorder is associated with concomitant cyanotic congenital heart disease, central nervous system anomalies, and esophageal atresia.

Goldenhar Syndrome: Rare disorder apparent at birth. Characterized by developmental abnormalities involving craniofacial anatomical structures, usually in a unilateral pattern. Malar hypoplasia, maxillary and mandibular hypoplasia, temporal hypoplasia, macrostomia, and cleft palate are present. In most cases, Goldenhar syndrome appears to occur randomly, with no apparent cause. Vertebral malformations may include vertebral hypoplasia, fusion, and/or absence of certain vertebrae. Many affected individuals may have additional skeletal, neurological, cardiac, pulmonary, renal, and/or gastrointestinal abnormalities.

Crane-Heise Syndrome: Severe lethal syndrome combining disproportionately large head with peculiar facies and bilateral talipes equinovarus.