Molecular and cellular bases of syndromic craniosynostoses.
Premature fusion of cranial sutures underlies the clinical condition of 'craniosynostosis', a common human disorder that occurs in both nonsyndromic and syndromic forms. The subgroup of syndromic craniosynostoses usually associates limb abnormalities and facial dysmorphism to skull distortion. Over the past decade, some of the genes causing these phenotypes have been identified. Among these, the gene encoding FGFR2, one of four members of the fibroblast growth factor receptor(FGFR) family, has been shown to account for several severe conditions including Apert, Pfeiffer, Crouzon, Beare-Stevenson and Jackson-Weiss syndromes. Two other FGFRs, FGFR1 and FGFR3, also account for craniosynostoses of variable severity [Pfeiffer, Crouzon with acanthosis nigricans (a pre-malignant skin disorder), and Muenke syndromes]. By contrast,Saethre-Chotzen syndrome and craniosynostosis (Boston-type) arise from mutations in the Twist and muscle segment homeobox 2 (MSX2) transcription factors, respectively. Whereas most FGFR mutations are likely to cause ligand independent activation of the receptor, leading to an upregulation of signaling pathways, mutations in the basic helix-loop-helix (bHLH) transcription factor Twist appear to induce loss of protein function. This review will summarise and discuss some of the cellular and molecular mechanisms involved in normal and abnormal craniofacial development, focusing on the possible interactions between the different factors controlling membranous ossification.
Bonaventure
Jacky
J
INSERM U 393, Hôpital Necker, 149 rue de Sèvres, 75743 Paris cedex 15, France. bonavent@necker.fr
El Ghouzzi
Vincent
V
D019465:Craniofacial Abnormalities / Q000235:genetics; D003398:Craniosynostoses / Q000209:etiology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors