Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature.
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.
Doherty
Emily S
ES
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Lacbawan
Felicitas
F
Hadley
Donald W
DW
Brewer
Carmen
C
Zalewski
Christopher
C
Kim
H Jeff
HJ
Solomon
Beth
B
Rosenbaum
Kenneth
K
Domingo
Demetrio L
DL
Hart
Thomas C
TC
Brooks
Brian P
BP
Immken
Ladonna
L
Lowry
R Brian
RB
Kimonis
Virginia
V
Shanske
Alan L
AL
Jehee
Fernanda Sarquis
FS
Bueno
Maria Rita Passos
MR
Knightly
Carol
C
McDonald-McGinn
Donna
D
Zackai
Elaine H
EH
Muenke
Maximilian
M
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
C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3