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The craniosynostosis syndromes are a group of disorders sharing the premature fusion of one or more sutures of the skull. Often additional anomalies are associated. There are eight craniosynostosis disorders caused by mutations in three fibroblast growth factor receptor genes: FGFR1, FGFR2 and FGFR3. All are autosomal dominant. Penetrance varies with the specific craniosynostosis type. Many FGFR mutations are associated with advanced paternal age.

Crouzon syndrome (MIM 123500) is one of the most common craniosynostosis syndromes. It is caused by mutations in the FGFR2 gene. Patients have coronal or multiple suture synostosis, resulting in brachycephaly, scaphocephaly or trigonocephaly. Other findings include maxillary hypoplasia, prognathism, a prominent beaked nose, downslanting palpebral fissures, shallow orbits and ocular proptosis. About one half of the cases are familial and one half are de novo, and correlate with increased paternal age. Intelligence is usually normal and brain abnormalities are rare, although progressive hydrocephalus does occur and may be associated with cerebellar herniation. Vision and hearing deficits occur. Fusion of cervical vertebrae is seen, but hands and feet appear normal although radiographs may reveal metacarpophalangeal profile shortening. Penetrance is typically complete but variable expressivity has been reported. The incidence is 1.6:100,000.