Fibroblast growth factor receptor mutations are associated with and, in fact, cause most syndromes presenting with
craniosynostosis. This knowledge has resulted in a shift in the paradigm of
suture fusion causation; it was thought previously that abnormal tensional forces arising in the cranial base caused fusion of the vault
sutures, but it is now understood that aberrant intercellular signaling in the developing skull leads to abnormal
suture morphogenesis. Although the mutations associated with these syndromes are known and the phenotypic consequences are well documented, the pathway from mutation to phenotype has yet to be elucidated. Surgical reconstruction is the primary treatment of
craniofacial abnormalities associated with craniosynostotic syndromes such as
Crouzon syndrome. In many cases, calvarial vault reshaping is dependent on the quality of the autologous bone available; however, the bone of patients with
craniosynostosis syndrome is often more brittle, thinner, and less robust than cranial bone from nonaffected donors. The relation between syndromic
craniosynostoses and this bone has not been previously described. In this study, the osteon and blood vessel diameters of calvarial bone from patients with
Crouzon syndrome and age- and sex-matched normal calvarial bone are measured. Statistical analysis demonstrates a quantitative and significant difference in the blood vessel diameter but not in the osteon diameter. This finding could be a result of abnormal blood vessel development caused by the
fibroblast growth factor receptor mutation occurring before and coincident with bone formation and leading to weakened and fragile bone tissue.