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Muenke Syndrome.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2006 May 10 [updated 2016 Nov 10].

Author information

National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Clinical Research Training Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, University of Kentucky, Lexington, Kentucky
Carilion Pediatric Clinic, Roanoke, Virginia



Muenke syndrome is defined by the presence of the specific FGFR3 pathogenic variant – c.749C>G – that results in the protein change p.Pro250Arg. Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pan synostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (reduced anteroposterior dimension of the skull), although turribrachycephaly (a "tower-shaped" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: temporal bossing; widely spaced eyes, ptosis or proptosis (usually mild); midface retrusion (usually mild); and highly arched palate or cleft lip and palate. Strabismus is common. Other findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); epilepsy; intracranial anomalies; intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family. Of note, some individuals who have the p.Pro250Arg pathogenic variant may have no signs of Muenke syndrome on physical or radiographic examination.


The diagnosis of Muenke syndrome is established by the identification of the FGFR3 pathogenic variant c.749C>G (p.Pro250Arg).


Treatment of manifestations: Children with Muenke syndrome and craniosynostosis are best managed by a pediatric craniofacial clinic that typically includes a craniofacial surgeon and neurosurgeon, clinical geneticist, ophthalmologist, otolaryngologist, pediatrician, radiologist, psychologist, dentist, audiologist, speech therapist, and social worker. Depending on severity, the first craniosynostosis repair (fronto-orbital advancement and cranial vault remodeling) is typically performed between ages three and six months. An alternative approach is endoscopic strip craniectomy, which is a less invasive procedure and is typically performed prior to age three months. Postoperative increased intracranial pressure and/or the need for secondary or tertiary extracranial contouring may occur. The need for secondary revision procedures is inversely related to the age of the affected individual at the time of initial repair. The location of the fused/synostotic suture, type of fixation, and the use of bone grafting do not have a significant effect on the need for revision. Standard treatments for sensorineural hearing loss; early speech therapy and intervention programs for those with developmental delay, intellectual impairment, behavioral problems, and/or hearing loss; surgical correction for strabismus; lubrication for exposure keratopathy. Prevention of secondary complications: Early surgical reconstruction for craniosynostosis may reduce the risk for complications including sequelae related to increased intracranial pressure (e.g., behavioral changes). Surveillance: Affected individuals benefit from integrated multidisciplinary care and protocol-driven management from birth to maturity that includes: annual multidisciplinary reviews and periodic review by a social work team; regular developmental assessments; periodic repeat audiograms to screen for acquired or progressive hearing loss; periodic assessment for strabismus.


Muenke syndrome is inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity. If the defining FGFR3 pathogenic variant cannot be detected in either parent of a proband, germline mosaicism in a parent or a de novo pathogenic variant in the proband are possible. Each child of an individual with Muenke syndrome has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant has been identified in the family. Prenatal ultrasound examination may be used as an adjunct to prenatal genetic testing.

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