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FGFR-Related Craniosynostosis Syndromes.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.
1998 Oct 20 [updated 2011 Jun 7].

Author information

Departments of Genetics and Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Fullerton Genetics Center, Asheville, North Carolina



The eight disorders comprising the FGFR-related craniosynostosis spectrum are Pfeiffer syndrome, Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, FGFR2-related isolated coronal synostosis, Jackson-Weiss syndrome, Crouzon syndrome with acanthosis nigricans (AN), and Muenke syndrome (isolated coronal synostosis caused by the p.Pro250Arg pathogenic variant in FGFR3). Muenke syndrome and FGFR2-related isolated coronal synostosis are characterized only by uni- or bicoronal craniosynostosis; the remainder are characterized by bicoronal craniosynostosis or cloverleaf skull, distinctive facial features, and variable hand and foot findings.


The diagnosis of Muenke syndrome is based on identification of the p.Pro250Arg pathogenic variant in FGFR3; the diagnosis of FGFR2-related isolated coronal synostosis is based on identification of a FGFR2 pathogenic variant. The diagnosis of the other six FGFR-related craniosynostosis syndromes is based on clinical findings; molecular genetic testing of FGFR1, FGFR2, and FGFR3 may be helpful in establishing the specific diagnosis in questionable cases.


Treatment of manifestations: Management by a multidisciplinary craniofacial clinic affiliated with a major pediatric medical center when possible; syndromic craniosynostosis usually requires a series of staged surgical procedures (craniotomy and fronto-orbital advancement) tailored to individual needs; for syndromic craniosynostosis, the first surgery is often as early as age three months, for nonsyndromic craniosynostosis the first surgery is often between ages six months and one year; congenital spine anomalies need immediate attention; surgical correction of limb defects depends on the nature of the skeletal anomalies. Prevention of secondary complications: Early treatment of craniofacial anomalies may reduce the risk for secondary complications such as hydrocephalus and cognitive impairment; ophthalmologic lubrication can prevent exposure keratopathy in those with severe proptosis. Surveillance: For hydrocephalus in those at increased risk. Evaluation of relatives at risk: Clinical and radiographic evaluation, or molecular genetic testing if the pathogenic variant in the family is known, so that mildly affected relatives can benefit from early intervention.


The FGFR-related craniosynostosis syndromes are inherited in an autosomal dominant manner. Affected individuals have a 50% chance of passing the pathogenic variant to each child. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant has been identified in the family; however, its use is limited by poor predictive value.

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