Quantification of Facial Skeletal Shape Variation in Fibroblast Growth Factor Receptor-Related Craniosynostosis Syndromes

Details

• Alternative Title:
  Birth Defects Res A Clin Mol Teratol
• Personal Author:
  Heuzé, Yann ; Martínez-Abadías, Neus ; Stella, Jennifer M. ; Arnaud, Eric ; Collet, Corinne ; Fructuoso, Gemma García ; Alamar, Mariana ; Lo, Lun-Jou ; Boyadjiev, Simeon A. ; Di Rocco, Federico ; Richtsmeier, Joan T.
• Description:
  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.
  
  
• Subjects:
  Amino Acid Substitution Article Craniosynostoses Diagnosis Facial Bones Female Genetic Diseases, Inborn Genotype-phenotype Correspondence Humans Infant Infant, Newborn Male Midfacial Retrusion Morphogenesis Mutation, Missense Receptor, Fibroblast Growth Factor, Type 2 Suture Fusion Syndrome

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• Source:
  Birth Defects Res A Clin Mol Teratol. 2014; 100(4):250-259.
• Pubmed ID:
  24578066
• Pubmed Central ID:
  PMC4029055
• Document Type:
  Journal Article
• Funding:
  3R01 DE18500-02S1/DE/NIDCR NIH HHS/United States ; 5R01 DD000350/DD/NCBDD CDC HHS/United States ; K23 DE000462/DE/NIDCR NIH HHS/United States ; K23 DE00462/DE/NIDCR NIH HHS/United States ; M01 RR00052/RR/NCRR NIH HHS/United States ; R01 DE016886/DE/NIDCR NIH HHS/United States ; R01 DE018500/DE/NIDCR NIH HHS/United States ; R01 DE022988/DE/NIDCR NIH HHS/United States ; R03 DE016342/DE/NIDCR NIH HHS/United States
• Volume:
  100
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:33ccfb0712200e66ea82c4247d3358ab18fb0d2e06382f8d9fecb491734a2bb6
• Download URL:
  https://stacks.cdc.gov/view/cdc/29963/cdc_29963_DS1.pdf
• File Type:
  [PDF - 511.90 KB ]