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

A. M. Howe*, A. H. Lipson, L. J. Sheffield, E. A. Haan, J. L. Halliday, F. Jenson, D. J. David, W. S. Webster

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)238-244
Number of pages7
JournalAmerican Journal of Medical Genetics
Issue number3
Publication statusPublished - 1995
Externally publishedYes


  • anticonvulsants
  • Binder 'syndrome'
  • chondrodysplasia punctata
  • embryopathy, warfarin
  • hydantoin
  • phenobarbitone
  • phenytoin
  • vitamin K deficiency

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