Prenatal exposure to phenytoin, facial development, and a possible role for vitamin K

Am J Med Genet. 1995 Sep 11;58(3):238-44. doi: 10.1002/ajmg.1320580309.


Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Drug-Induced*
  • Adult
  • Anticonvulsants / adverse effects*
  • Child
  • Chondrodysplasia Punctata / chemically induced*
  • Chondrodysplasia Punctata / prevention & control
  • Face / abnormalities*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Phenytoin / adverse effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Vitamin K / administration & dosage*
  • Vitamin K / therapeutic use
  • Vitamin K Deficiency / chemically induced
  • Vitamin K Deficiency / prevention & control


  • Anticonvulsants
  • Vitamin K
  • Phenytoin