title: FGFR3 P250R mutation increases the risk of reoperation in apparent 'nonsyndromic' coronal craniosynostosis.
abstract: 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.
authors.affiliation: Oxford Craniofacial Unit, Radcliffe Infirmary, Oxford, United Kingdom.
authors.forename: Gregory P L
authors.initials: GP
authors.lastname: Thomas
authors.forename: Andrew O M
authors.initials: AO
authors.lastname: Wilkie
authors.forename: Peter G
authors.initials: PG
authors.lastname: Richards
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wall
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000235:genetics* / Q000601:surgery; D003399:Craniotomy / Q000009:adverse effects; D005260:Female; D006579:Heterozygote; D006801:Humans; D019586:Intracranial Hypertension / Q000209:etiology / Q000601:surgery; D008297:Male; D017354:Point Mutation; D011392:Proline / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012086:Reoperation; D012189:Retrospective Studies; D013577:Syndrome
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D001120:Arginine; D011392:Proline; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3