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Title: Holoprosencephaly and genitourinary anomalies in fetal methotrexate syndrome
Author: Corona-Rivera, J.R.
Rea-Rosas, A.
Santana-Ramirez, A.
Acosta-Leon, J.
Hernandez-Rocha, J.
Miguel-Jimenez, K.
Issue Date: 2010
Abstract: Prenatal exposure to methotrexate (MTX) in the first trimester may leadtofetal death, and surviving childrenhave increasedrisks for cranial dysostosis, dysmorphic facies, skeletal malformations, limb defects, growth retardation, and, in somecases, developmental delay, a pattern of defects recognized as fetal MTX syndrome (FMS).Wereport on amale infantwho, inadditionto severe FMS, showed previously undescribed central nervous system(CNS) and genitourinary anomalies that contributed to the further delineation. The propositus was born to a G2, 20-year-oldmother with an irregular menstrual history. The unplanned pregnancy was complicated by oral MTX treatment (5mg/day) for suspected systemic lupus erythematosus for 14 days at the 5th week post-conception, as dated by the first trimester sonogram. In addition to the typical features of the FMS, our propositus exhibited congenital penile curvature, vesicoureteral reflux, hydronephrosis, and severe CNS anomalies including semilobar holoprosencephaly (HPE). A single previous report of lobar-type HPE in an infant with FMS led us to confirm that the HPE observed in the propositus is a feature attributable to MTX teratogenicity, although the exact mechanisms of the HPE production need to be further elucidated. Also, this case serves to highlight the presence of genitourinary anomalies in patients with FMS, a fact that requires intentional searches in future patients in order to confirmthis asbeing characteristic of the entity. © 2010 Wiley-Liss, Inc.
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