Pathology of Syndromic Craniosynostosis in Children

Pathophysiology

• Fusion starts at single point: Albright and Byrd determined that craniosynostosis starts at a single point at the inferior part of each suture and then spreads along the affected suture (19).
• Fusion prevents normal growth in infant: Premature fusion of craniofacial sutures hinders normal displacement between the bones involved, leading to an abnormal growth pattern. Fusion of the calvarial sutures therefore primarily affects the infant or young child, whereas premature synostosis of the cranial base continues to be relevant into late adolescence.
• Compensatory growth accentuates abnormal growth: An important principle of craniofacial growth is the fact that if the growth of a specific system is impaired, another system can assume its role as a compensatory mechanism.
• Virchow’s concept that deformity is secondary: Virchow thought that the synostosis of the calvarial sutures was a primary malformation and cranial base deformities were secondary (3). However, there is increasing evidence that the cartilaginous cranial base is primarily involved in both Crouzon and Apert syndromes (20, 21, 22, 23). Controversy remains whether the synostoses of the calvarial sutures in these syndromes are secondary to the anomaly of the cranial base or are the result of a biochemical defect (24, 25).

Molecular/Genetic Pathology

see Genetic Mutations and Syndromic Craniosynostosis

• Dominantly inherited syndromes: Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen, Cranio-fronto-nasal syndrome (x-linked), Jackson-Weiss, and Boston syndromes are examples of syndromic craniosynostoses that are autosomal dominant.
• Recessively inherited syndromes: Carpenter, Antley-Bixler, and Baller-Gerold syndromes are examples of syndromic craniosynostoses that are autosomal recessive.
• FGFR: Mutations of the genes responsible for synthesis of FGFR and other factors have been associated with multiple types of syndromic craniosynostosis.