Quantification of facial skeletal shape variation in fibroblast growth factor receptor-related craniosynostosis syndromes

Yann Heuzé, Neus Martínez-Abadías, Jennifer M. Stella, Eric Arnaud, Corinne Collet, Gemma García Fructuoso, Mariana Alamar, Lun Jou Lo, Simeon A. Boyadjiev, Federico Di Rocco, Joan T. Richtsmeier

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background: fibroblast growth factor receptor (FGFR) -related craniosynostosis syndromes are caused by many different mutations within FGFR-1, 2, 3, and certain FGFR mutations are associated with more than one clinical syndrome. These syndromes share coronal craniosynostosis and characteristic facial skeletal features, although Apert syndrome (AS) is characterized by a more dysmorphic facial skeleton relative to Crouzon (CS), Muenke (MS), or Pfeiffer syndromes. Methods: Here we perform a detailed three-dimensional evaluation of facial skeletal shape in a retrospective sample of cases clinically and/or genetically diagnosed as AS, CS, MS, and Pfeiffer syndrome to quantify variation in facial dysmorphology, precisely identify specific facial features pertaining to these four syndromes, and further elucidate what knowledge of the causative FGFR mutation brings to our understanding of these syndromes. Results: Our results confirm a strong correspondence between genotype and facial phenotype for AS and MS with severity of facial dysmorphology diminishing from Apert FGFR2S252W to Apert FGFR2P253R to MS. We show that AS facial shape variation is increased relative to CS, although CS has been shown to be caused by numerous distinct mutations within FGFRs and reduced dosage in ERF. Conclusion: Our quantitative analysis of facial phenotypes demonstrate subtle variation within and among craniosynostosis syndromes that might, with further research, provide information about the impact of the mutation on facial skeletal and nonskeletal development. We suggest that precise studies of the phenotypic consequences of genetic mutations at many levels of analysis should accompany next-generation genetic research and that these approaches should proceed cooperatively.

Original languageEnglish (US)
Pages (from-to)250-259
Number of pages10
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Issue number4
StatePublished - Apr 2014

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Developmental Biology


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