Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature.

Abstract

Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings in Muenke syndrome. To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. We reviewed audiograms from an additional 13 patients with Muenke syndrome. A majority of the patients (95%) demonstrated a mild-to-moderate, low frequency sensorineural hearing loss. This pattern of hearing loss was not previously recognized as characteristic of Muenke syndrome. We also report on feeding and swallowing difficulties in children with Muenke syndrome. Combining 312 reported cases of Muenke syndrome with data from the nine NIH patients, we found that females with the Pro250Arg mutation were significantly more likely to be reported with craniosynostosis than males (P < 0.01). Based on our findings, we propose that the clinical management should include audiometric and developmental assessment in addition to standard clinical care and appropriate genetic counseling.

• Authors: Emily S Doherty, Felicitas Lacbawan, Donald W Hadley, Carmen Brewer, Christopher Zalewski, H Jeff Kim, Beth Solomon, Kenneth Rosenbaum, Demetrio L Domingo, Thomas C Hart, Brian P Brooks, Ladonna Immken, R Brian Lowry, Virginia Kimonis, Alan L Shanske, Fernanda Sarquis Jehee, Maria Rita Passos Bueno, Carol Knightly, Donna McDonald-McGinn, Elaine H Zackai, Maximilian Muenke
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 143A Issue 24 Pg. 3204-15 (Dec 15 2007) ISSN: 1552-4833 [Electronic] United States
• PMID: 18000976 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• FGFR3 protein, human
• Receptor, Fibroblast Growth Factor, Type 3

Topics

• Adult
• Aged
• Audiometry (methods)
• Child, Preschool
• Craniosynostoses (diagnosis, genetics)
• Developmental Disabilities (diagnosis, genetics)
• Female
• Hearing Loss, Sensorineural (diagnosis, genetics)
• Humans
• Infant
• Male
• Mutation
• Pedigree
• Phenotype
• Receptor, Fibroblast Growth Factor, Type 3 (genetics)
• Sex Factors
• Speech Disorders (diagnosis, genetics)
• Syndrome
• Tomography, X-Ray Computed (methods)