title: 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.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Doherty
authors.forename: Felicitas
authors.initials: F
authors.lastname: Lacbawan
authors.forename: Donald W
authors.initials: DW
authors.lastname: Hadley
authors.forename: Carmen
authors.initials: C
authors.lastname: Brewer
authors.forename: Christopher
authors.initials: C
authors.lastname: Zalewski
authors.forename: H Jeff
authors.initials: HJ
authors.lastname: Kim
authors.forename: Beth
authors.initials: B
authors.lastname: Solomon
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rosenbaum
authors.forename: Demetrio L
authors.initials: DL
authors.lastname: Domingo
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Hart
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.forename: Ladonna
authors.initials: L
authors.lastname: Immken
authors.forename: R Brian
authors.initials: RB
authors.lastname: Lowry
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
authors.forename: Alan L
authors.initials: AL
authors.lastname: Shanske
authors.forename: Fernanda Sarquis
authors.initials: FS
authors.lastname: Jehee
authors.forename: Maria Rita Passos
authors.initials: MR
authors.lastname: Bueno
authors.forename: Carol
authors.initials: C
authors.lastname: Knightly
authors.forename: Donna
authors.initials: D
authors.lastname: McDonald-McGinn
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000328:Adult; D000368:Aged; D001299:Audiometry / Q000379:methods; D002675:Child, Preschool; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics*; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D012737:Sex Factors; D013064:Speech Disorders / Q000175:diagnosis / Q000235:genetics; D013577:Syndrome; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3