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.
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Coronal synostosis has a worse prognosis-more repeat surgery and persistent deformity-when the Muenke syndrome mutation is present.
“coronal synostosis has a worse prognosis (higher risk of repeat surgery and persistent deformity) in the presence of the Muenke syndrome mutation; 48,49”
From Craniosynostosis (2011) · cites this paper as [48]
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Cobourne, M. T., & Rice, D. P. C. (2016) · Wiley eBooks · doi:10.1002/9781119004370.ch55
Gripp, K. W., & Zackai, E. H. (2010) · doi:10.1002/9780470893159.ch17
Graham, J. M. (2007) · Elsevier eBooks · doi:10.1016/b978-072161489-2.10031-1
Rachwalski, M. (2021) · Springer eBooks · doi:10.1007/978-3-030-72338-5_19
Genetic Features of Craniosynostosis
Tahta, A., Turgut, M., & Hall, W. A. (2021) · Springer eBooks · doi:10.1007/978-3-030-72338-5_15
February’s 2019 Full Issue PDF
(2019) · Journal of Diagnostics and Treatment of Oral and Maxillofacial Pathology · doi:10.23999/j.dtomp.2019.2.full
Graham, J. M., & Sanchez-Lara, P. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-11414-4.00031-4
- Authors
- Thomas, G. P. L., Wilkie, A. O. M., Richards, P. G., & Wall, S. A.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Thomas, Gregory P. L
- Richards, Peter G
- Wall, Steven A
- Venue
- Journal of Craniofacial Surgery
- Published
- 2005-05
- Volume
- 16
- Issue
- 3
- Pages
- 347-352
- ISSN
- 1049-2275 (ISSN-L)
- OpenAlex
- W2132893438
- Cited by
- 58
- References
- 39
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 2 · 2016: 3 · 2014: 2 · 2013: 1 · 2012: 4
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Craniofacial Surgery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Health Sciences › Medicine › Surgery › Pectus Deformity Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Reconstructive Facial Surgery Techniques
- Keywords
- coronal craniosynostosis, nonsyndromic craniosynostosis, reoperation, transcranial surgery, heterozygosity, intracranial hypertension, genetic analysis, long-term follow-up
- MeSH terms
- Adolescent, Arginine, Child, Child, Preschool, Craniosynostoses, Craniotomy, Female, Heterozygote, Humans, Male, Proline, Protein-Tyrosine Kinases, Reoperation, Retrospective Studies, Syndrome, Point Mutation, Receptors, Fibroblast Growth Factor, Intracranial Hypertension, Amino Acid Substitution, Receptor, Fibroblast Growth Factor, Type 3
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