Apert syndrome

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.

Apert syndrome (MIM 101200) is a relatively severe form of FGFR2 related craniosynostosis with numerous organ systems being affected. Findings in Apert syndrome include turribrachycephalic skull shape a wide open anterior fontanelle at birth, broad thumbs and great toes that deviate away from the other digits, variable syndactyly of hands and feet, but involving at least the central 3 digits of the hands, incomplete postaxial polydactyly of the hands and preaxial polydactyly of the feet, progressive synostosis of the cervical vertebrae, and bones of the hands and feet. Typical FGFR related craniosynostosis findings include midface hypoplasia, mandibular prognathism, cleft palate, small beaked nose, hypertelorism, ocular proptosis and other ocular abnormalities. Central nervous system abnormalities with variable degrees of intellectual disability occur in 50% of patients. Cutaneous manifestations include acne, hyperhidrosis, hyperkeratosis and hypopigmentation among others. The majority of cases are sporadic and the prevelance is 1:65,000 to 1:100,000. Penetrance is complete.