title: Quantification of facial skeletal shape variation in fibroblast growth factor receptor-related craniosynostosis syndromes.
abstract: 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 FGFR2(S252W) to Apert FGFR2(P253R) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Yann
authors.initials: Y
authors.lastname: Heuzé
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Abadías
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Stella
authors.forename: Eric
authors.initials: E
authors.lastname: Arnaud
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.forename: Gemma
authors.initials: G
authors.lastname: García Fructuoso
authors.forename: Mariana
authors.initials: M
authors.lastname: Alamar
authors.forename: Lun-Jou
authors.initials: LJ
authors.lastname: Lo
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
authors.forename: Federico
authors.initials: F
authors.lastname: Di Rocco
authors.forename: Joan T
authors.initials: JT
authors.lastname: Richtsmeier
mesh_terms: D019943:Amino Acid Substitution; D003398:Craniosynostoses / Q000235:genetics / Q000473:pathology; D005147:Facial Bones / Q000002:abnormalities*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D013577:Syndrome
chemical_list: C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: diagnosis; genotype-phenotype correspondence; midfacial retrusion; morphogenesis; suture fusion