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Pfeiffer 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.

Pfeiffer syndrome (MIM 101600) patients have craniosynostosis with broad thumbs and/or great toes that are medially deviated.  Brachydactyly and variable degrees of syndactyly may occur.  Pfeiffer syndrome has been divided into three subtypes.  Type 1 is clinically the least severe and has the best prognosis. Patients have bicoronal craniosynostosis, moderate to severe midface hypoplasia and they usually have a normal life span and normal intelligence. About 5% of Pfeiffer syndrome type 1 patients have a specific FGFR1 mutation and about 95% have FGFR2 mutations. Pfeiffer syndrome type 2 patients have cloverleaf skulls, severe ocular proptosis, neurodevelopmental problems, elbow and knee ankylosis and foreshortened life spans. Type 3 is similar to type 2 but the skull is turribrachycephalic and patients also die young.  Type 2 and Type 3 are caused by FGFR2 mutations. Penetrance is complete and expressivity is variable in Pfeiffer syndrome.  Sporadic as well as familial cases occur. The prevalence of Pfeiffer syndrome is estimated as 1:100,000.