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Craniosynostosis Following Fetal Methotrexate Exposure

Zarella, Christopher S. MD; Albino, Frank P. MD; Oh, Albert K. MD; Wood, Benjamin C. MD; Oluigbo, Chima O. MD; Myseros, John S. MD; Magge, Suresh N. MD; Keating, Robert F. MD; Rogers, Gary F. MD, MPH

Journal of Craniofacial Surgery: March 2016 - Volume 27 - Issue 2 - p 450–452
doi: 10.1097/SCS.0000000000002423
Clinical Studies

Methotrexate (MTX) is an antimetabolite, folic acid antagonist that inhibits purine nucleotide production, DNA synthesis, and cellular proliferation. Despite widespread therapeutic uses, MTX remains a potent teratogen. Methotrexate embryopathy encompasses multiorgan system dysfunction, including intrauterine growth restriction as well as cardiac, craniofacial, renal, genital, and skeletal abnormalities. Effects of MTX exposure on fetal development continue to be described. This series of 4 patients with MTX-associated craniosynostosis represents the largest published association between prenatal MTX exposure and premature cranial suture closure.

*Department of Neurosurgery, Division of Plastic Surgery, Children's National Medical Center, Washington, DC.

Address correspondence and reprint requests to Gary F. Rogers, MD, Children's National Medical Center, 111 Michigan Ave NW, West Wing, 4th Floor, Suite 100, Washington, DC 20010; E-mail:

Received 7 August, 2015

Accepted 30 November, 2015

The authors report no conflicts of interest.

© 2016 by Mutaz B. Habal, MD.