PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 
years ago, represents the single most common craniosynostosis mutation. Muenke 
syndrome is characterized by coronal suture synostosis, midface hypoplasia, 
subtle limb anomalies, and hearing loss. However, the spectrum of clinical 
presentation continues to expand. To better understand the pathophysiology of 
the Muenke syndrome, we present collective findings from several recent studies 
that have characterized a genetically equivalent mouse model for Muenke syndrome 
(FgfR3 (P244R)) and compare them with human phenotypes.
CONCLUSIONS: FgfR3 (P244R) mutant mice show premature fusion of facial sutures, 
premaxillary and/or zygomatic sutures, but rarely the coronal suture. The mice 
also lack the typical limb phenotype. On the other hand, the mutant mice display 
maxillary retrusion in association with a shortening of the anterior cranial 
base and a premature closure of intersphenoidal and spheno-occipital 
synchondroses, resembling human midface hypoplasia. In addition, sensorineural 
hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of 
Muenke syndrome patients. It is caused by a defect in the mechanism of cell fate 
determination in the organ of Corti. The mice also express phenotypes that have 
not been previously described in humans, such as reduced cortical bone 
thickness, hypoplastic trabecular bone, and defective temporomandibular joint 
structure. Therefore, the FgfR3 (P244R) mouse provides an excellent opportunity 
to study disease mechanisms of some classical phenotypes of Muenke syndrome and 
to test novel therapeutic strategies. The mouse model can also be further 
explored to discover previously unreported yet potentially significant 
phenotypes of Muenke syndrome.