FGFR3 P250R mutation increases the risk of reoperation in apparent 'nonsyndromic' coronal craniosynostosis

J Craniofac Surg. 2005 May;16(3):347-52; discussion 353-4. doi: 10.1097/01.scs.0000157024.56055.f2.


Many patients with a clinical diagnosis of "nonsyndromic" coronal craniosynostosis have been found to be heterozygous for the fibroblast growth factor receptor 3 (FGFR3) mutation Pro250Arg. The phenotype associated with this mutation is variable and lacks highly distinctive features, so it is difficult to diagnose on clinical examination alone. The authors present a retrospective study of 76 patients with isolated coronal synostosis who were operated on in a single dedicated craniofacial unit over 25 years. The authors investigated whether any single factor, including the presence of a FGFR3 Pro250Arg mutation, predisposed to an increased transcranial reoperation rate. Eight patients had repeat transcranial surgery for a functional indication. Heterozygosity for the FGFR3 Pro250Arg mutation, present in 29 patients in the cohort, was the only factor found to have a significant association (P=0.048) with the transcranial reoperation rate. Six patients (20.7%) with the mutation underwent reoperation on the basis of raised intracranial pressure, as compared with two patients (4.3%) without the mutation. This highlights the need for genetic analysis and long-term clinical follow-up in apparently "isolated" coronal synostosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Substitution / genetics
  • Arginine / genetics
  • Child
  • Child, Preschool
  • Craniosynostoses / genetics*
  • Craniosynostoses / surgery
  • Craniotomy / adverse effects
  • Female
  • Heterozygote
  • Humans
  • Intracranial Hypertension / etiology
  • Intracranial Hypertension / surgery
  • Male
  • Point Mutation
  • Proline / genetics
  • Protein-Tyrosine Kinases / genetics*
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*
  • Reoperation
  • Retrospective Studies
  • Syndrome


  • Receptors, Fibroblast Growth Factor
  • Arginine
  • Proline
  • FGFR3 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 3