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Muenke syndrome (MNKES) - 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.

Muenke syndrome (MNKES; MIM 602849) is caused by a specific FGFR3 mutation, Pro250Arg.  The phenotypic presentation in Muenke syndrome is variable and patients may be misdiagnosed with another craniosynostosis syndrome.  Clinical findings include unicoronal or bicoronal craniosynostosis, midface hypoplasia, downslanting palpebral fissures and ptosis. Unicoronal synostosis is more frequent in males.  Bone abnormalities of the hands and feet may occur. Some carriers of the FGFR3 mutation do not have craniosynostosis, but may only have macrocephaly or even normal sized heads. Sensorineural hearing loss is seen in about one-third of the patients. Mild mental retardation can occur. Intrafamilial variation is great. The mutation rate is similar to that observed with achondroplasia, and the prevelance is estimated to be 1:30,000. Penetrance is incomplete.