title: Clinical dividends from the molecular genetic diagnosis of craniosynostosis.
abstract: A dozen years have passed since the first genetic lesion was identified in a family with craniosynostosis, the premature fusion of the cranial sutures. Subsequently, mutations in the FGFR2, FGFR3, TWIST1, and EFNB1 genes have been shown to account for approximately 25% of craniosynostosis, whilst several additional genes make minor contributions. Using specific examples, we show how these discoveries have enabled refinement of information on diagnosis, recurrence risk, prognosis for mental development, and surgical planning. However, phenotypic variability can present a significant challenge to the clinical interpretation of molecular genetic tests. In particular, the difficulty of analyzing the complex interaction of genetic background and prenatal environment in determining clinical features, limits the value of identifying low penetrance mutations.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. awilkie@hammer.imm.ox.ac.uk
authors.forename: Andrew O M
authors.initials: AO
authors.lastname: Wilkie
authors.forename: Elena G
authors.initials: EG
authors.lastname: Bochukova
authors.forename: Ruth M S
authors.initials: RM
authors.lastname: Hansen
authors.forename: Indira B
authors.initials: IB
authors.lastname: Taylor
authors.forename: Sahan V
authors.initials: SV
authors.lastname: Rannan-Eliya
authors.forename: Jo C
authors.initials: JC
authors.lastname: Byren
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wall
authors.forename: Lina
authors.initials: L
authors.lastname: Ramos
authors.forename: Margarida
authors.initials: M
authors.lastname: Venâncio
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hurst
authors.forename: Anthony W
authors.initials: AW
authors.lastname: O'rourke
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Williams
authors.forename: Anneke
authors.initials: A
authors.lastname: Seller
authors.forename: Tracy
authors.initials: T
authors.lastname: Lester
mesh_terms: D000328:Adult; D002675:Child, Preschool; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D010375:Pedigree; D011379:Prognosis