Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction.
Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of
craniosynostosis. Nonsyndromic
craniosynostosis accounts for more than 70% of all cases. Syndromic
craniosynostosis with a certain genetic cause is more likely to involve multiple
sutures or bilateral coronal
sutures. FGFR2, FGFR3, FGFR1, TWIST1 and
EFNB1 genes are major causative genes of genetic syndromes associated with
craniosynostosis. Although most of syndromic
craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases.
Apert syndrome,
Pfeiffer syndrome,
Crouzon syndrome, and
Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes.
Saethre-Chotzen syndrome,
Muenke syndrome, and
craniofrontonasal syndrome are representative disorders showing isolated coronal
suture involvement. Compared to the other types of
craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal
synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic
craniosynostosis.