Details:

Alternative Title:
Birth Defects Res A Clin Mol Teratol
Publisher's site:
http://dx.doi.org/10.1002/bdra.23228
Personal Author:
Heuzé, Yann ; Martínez-Abadías, Neus ; Stella, Jennifer M. ; Arnaud, Eric ; Collet, Corinne ; ... More +
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. ; Less -
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.
Subject:
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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

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 ; ... More +
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 DE016886/DE/NIDCR NIH HHS/United States ; R01 DE018500/DE/NIDCR NIH HHS/United States ; R01 DE018500/DE/NIDCR NIH HHS/United States ; R01 DE022988/DE/NIDCR NIH HHS/United States ; R01 DE022988/DE/NIDCR NIH HHS/United States ; R03 DE016342/DE/NIDCR NIH HHS/United States ; Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:33ccfb0712200e66ea82c4247d3358ab18fb0d2e06382f8d9fecb491734a2bb6
File Type:

Supporting Files

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