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| Syndrome | fetal aminopterin syndrome |
|---|---|
| Synonyms | aminopterin embryopathy syndrome |
| aminopterin fetopathy syndrome | |
| aminopterin syndrome | |
| fetal methotrexate syndrome | |
| MeSH | Abnormalities, Drug-Induced |
| Aminopterin / adverse effects | |
| Bone and Bones / abnormalities | |
| Brain / abnormalities | |
| Craniofacial Abnormalities | |
| Fetus / drug effects | |
| Growth Disorders | |
| Methotrexate / adverse effects | |
| Summary | Multiple anomalies in infants after failed abortion with aminopterin and methotrexate. The most common anomalies include growth deficiency, craniofacial deformities (patent cranial sutures, craniosynostosis, unusual skull shape, dysmorphic facies and other defects), central nervous system (hydrocephalus and mental retardation), and skeletal defects (stenotic long bones, syndactyly, and talipes equinovarus. A syndrome closely resembling or identical to the aminopterin embryopathy syndrome, without exposure to antifolate drugs, is referred to as the aminopterin-like syndrome without aminopterin. |
| Major Features | Head and neck: Dysmorphic facies, cranial dysplasia, open cranial sutures, craniolacunae, craniosynostosis, deficient skull ossification, wormian bones, cranium bifidum, aberrant suture of the parietal bones, micrognathia, and abnormal skull shape. |
| Ears: Low-set ears. | |
| Eyes: Hypertelorism, prominent eyes, and shallow supraorbital ridges. | |
| Nose: Broad nasal bridge and epicanthal folds. | |
| Mouth and oral structures: Cleft palate in some cases. | |
| Thorax: Rib abnormalities. | |
| Hand and foot: Talipes equinovarus, brachydactyly, syndactyly, and absence or hypoplasia of fingers or toes. | |
| Extremities: Stenotic long bones, micromelia or mesomelia and hip dislocation. | |
| Spine: Spina bifida may occur. | |
| Skin appendages: Upsweep of hair on the forehead. | |
| Nervous system: Hydrocephalus and occasional anencephaly and neural tube defects. | |
| Growth and development: Growth and mental retardation. | |
| Behavior and performance: Myopia. | |
| Etiology and pathogenesis: Teratogenic effects of folic acid antagonists (aminopterin and methotrexate). | |
| Historical References | Giroud A, Lefebvres-Boisselot J Influence tératogène de la carence en acide folique. C Rend Soc Biol (Paris), 1951, 145:526 |
| Meltzer HJ Congenital anomalies due to attempted abortion with 4-pteroylglutamic acid. JAMA, 1956, 161:1253 | |
| Nelson MM et al Production of multiple congenital abnormalities in young by maternal pteroylglutamic acid deficiency during gestation. J Nutrition, 1952, 48:61 | |
| Thiersch JB Therapeutic abortions with a folic acid antagonist, 4-pteroylglutamic acid (4-amino P.G.A.) administered by the oral route. Am J Obst Gyn, 1952, 63:1298-1304 | |
| Warkany J et al Attempted abortion with aminopterin (4-aminopteroylglutamic acid). Malformations of a child. J Dis Child, 1959, 97:274-81 | |
| Bibliography | Baranov VS Characteristics of the teratogenic effect of aminopterin compared with that of other teratogenic agents. Bull Exp Biol Med (USSR), 1966, 61:77-81 |
| Brandner M, Nusslé D Embryopathie due to l'aminoptérine avec sténose congénitale de l'espace médullaire des os tubulaire longs. Ann Radiol (Paris), 1969, 12:703-10 | |
| Char P Aminopterin embryopathy syndrome. Am J Dis Child, 1979, 133:1189-90 | |
| de Alvarez RR An evaluation of aminopterin as an abortifacient. Am J Obst Gyn, 1962, 83:1476-7 | |
| Dobbing J Pregnancy and leukemia. Lancet, 1977, 1:1155 | |
| Emerson DJ Congenital malformations due to attempted abortion with aminopterin. Am J Obst Gyn, 1962, 84:356-7 | |
| Gellis SS, Feingold M Aminopterin embryopathy syndrome. Am J Dis Child, 1979, 133:1189-90 | |
| Gilliland J, Weinstein L The effects of cancer chemotherapeutic agents on developing fetus. Cancer Res, 1983, 38:6-13 | |
| Goetsch C An evaluation of aminopterin as an abortifacient. Am J Obst Gyn, 1962, 83:1474-7 | |
| Grella P et al Antineoplastici e gravidanza. Minerva Med, 1984, 75:1643-9 | |
| Hibbard BM Folates and the fetus. S Afr Med J, 1975, 49:1223-6 | |
| Howard NJ, Rudd NL The natural history of aminopterin-induced embryopathy. Birth Defects, 1977, 13(3C):85-93 | |
| Milunsky A et al Methotrexate-induced congenital malformations. J Pediat, 1968, 72:790-5 | |
| Nicholson HO Cytotoxic drugs in pregnancy: Review of reported cases. J Obst Gyn Brit Comm, 1968, 75:307-12 | |
| Perry W Methotrexate and teratogenesis. Arch Derm, 1983, 119:874-5 | |
| Pizzuto J et al Treatment of acute leukemia during pregnancy: Presentation of nine cases. Cancer Treat Rep, 1980, 64:679-83 | |
| Powell HR, Ekert H Methotrexate-induced congenital malformations. Med J Austral, 1971, 2:1076-7 | |
| Reich EW et al Recognition in adult patients of malformations induced by folic-acid antagonists. Birth Defects, 1977, 14(6B):139-60 | |
| Shaw EB Fetal damage due to maternal aminopterin ingestion. Follow-up at 9 years of age. Am J Dis Child, 1972, 124:93-4 | |
| Shaw EB, Reese EL Fetal damage due to maternal aminopterin ingestion: Follow-up at 17-1/2 years of age. Am J Dis Child, 1980, 134:1172-3 | |
| Shaw EB, Steinbach HL Aminopterin-induced fetal malformations: Survival of an infant after attempted abortion. Am J Dis Child, 1968, 115:477-82 | |
| Sieber S, Adamson R Toxicity of antineoplastic agents in man: Chromosome aberrations, antifertility effects, congenital malformations, and carcinogenic potential. Adv Cancer Res, 1975, 22:57-155 | |
| Voorhees JJ et al Cytogenetic evaluation of methotrexate-treated psoriatic patients. Arch Derm, 1969, 100:269-74 | |
| Warkany J Aminopterin and methotrexate: Folic acid deficiency. Teratology, 1978, 17:353-8 | |
| Warkany J Teratogenicity of folic acid antagonists. Cancer Bull, 1981, 33:76-7 | |
| Werthemann A Algemeine und spezielle Probleme bei der Analyse von Missbildungsurschen, in Sonderheit bei Thalidamid- und Aminopterin-schäden. Schweiz Med Wschr, 1963, 93:223-7 |