Apparent cyclophosphamide (cytoxan) embryopathy: A distinct phenotype?

Cyclophosphamide (CP) is an alkylating agent widely used in treating cancer and autoimmune disease. CP is classified as a pregnancy risk factor D drug and is teratogenic in, animals, but population studies have not conclusive ly demonstrated teratogenicity in::humans. Six isolated reports of prenatal ly exposed infants with various congenital anomalies exist, but to date no specific phenotype has been delineated. The purpose of this report is to do cument a new case of: in utero CP exposure with multiple congenital anomali es and to establish an apparent CP embryopathy phenotype. The mother had sy stemic lupus erythematosus and cyclophosphamide exposure in the first trime ster. She also took nifedipine, atenolol, clonidine, prednisone, aspirin, a nd potassium chloride throughout pregnancy. The infant had growth retardati on and multiple anomalies including microbrachycephaly, coronal craniosynos tosis, hypotelorism, shallow orbits, proptosis, blepharophimosis, :small, a bnormal ears, unilateral preauricular pit, broad, flat nasal bridge, micros tomia, high-arched palate, micrognathia, preaxial upper limb and postaxial lower limb defects consisting of hypoplastic thumbs, and bilateral absence of the 4th and 5th toes. Chromosomes were apparently normal. The reported c ases of in utero exposure to cyclosposphamide shared the following manifest ations with our patient: growth deficiency, developmental delay, craniosyno stosis, blepharophimosis, flat nasal bridge, abnormal ears, and distal limb defects including hypoplastic thumbs and oligodactyly.: We conclude that ( a) cyclophosphamide is a human teratogen, (b) a distinct phenotype exists, and (c) the safety of CP in pregnancy is in serious question. (C) 1999 Wile y-Liss, Inc.