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

• Published in: American journal of medical genetics. Part A Vol. 143A; no. 24; pp. 3204 - 3215
• Main Authors: Doherty, Emily S., Lacbawan, Felicitas, Hadley, Donald W., Brewer, Carmen, Zalewski, Christopher, Kim, H. Jeff, Solomon, Beth, Rosenbaum, Kenneth, Domingo, Demetrio L., Hart, Thomas C., Brooks, Brian P., Immken, LaDonna, Lowry, R. Brian, Kimonis, Virginia, Shanske, Alan L., Jehee, Fernanda Sarquis, Bueno, Maria Rita Passos, Knightly, Carol, McDonald-McGinn, Donna, Zackai, Elaine H., Muenke, Maximilian
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.12.2007; Wiley-Liss
• Subjects: Adult; Aged; Audiometry - methods; Biological and medical sciences; Child, Preschool; coronal suture synostosis; Craniosynostoses - diagnosis; Craniosynostoses - genetics; craniosynostosis; developmental delay; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; Diseases of the osteoarticular system; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Female; fibroblast growth factor receptor 3; hearing loss; Hearing Loss, Sensorineural - diagnosis; Hearing Loss, Sensorineural - genetics; Humans; Infant; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Muenke syndrome; Mutation; Non tumoral diseases; Otorhinolaryngology. Stomatology; Pedigree; Phenotype; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Sex Factors; speech delay; Speech Disorders - diagnosis; Speech Disorders - genetics; Syndrome; Tomography, X-Ray Computed - methods; Fibroblast growth factor; Nervous system diseases; Muenke syndrome; Craniosynostosis; Diseases of the osteoarticular system; Synostosis; fibroblast growth factor receptor 3; Auditory disorder; Dysostosis; Developmental disorder; coronal suture synostosis; Syndrome; Hearing loss; Phenotype; Growth factor receptor; Language retardation; Skull disease; speech delay; ENT disease; developmental delay; Expansion; Bibliographic review
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32078

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. Published 2007 Wiley‐Liss, Inc.