Hearing Loss in Syndromic Craniosynostoses: Introduction and Consideration of Mechanisms Purpose There are a number of craniosynostosis syndromes with hearing loss—including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes—that result from mutations in the fibroblast growth factor receptor (FGFR) genes. Studies of FGFRs and their ligands, fibroblast growth factors (FGFs), have revealed clues to the precise ... Review Article
Review Article  |   June 01, 2014
Hearing Loss in Syndromic Craniosynostoses: Introduction and Consideration of Mechanisms
 
Author Affiliations & Notes
  • Nneamaka B. Agochukwu
    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
    Clinical Research Training Program, National Institutes of Health, Bethesda, MD
  • Benjamin D. Solomon
    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
  • Maximilian Muenke
    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
  • Disclosure: The authors have declared that no competing interests existed at the time of publication.
    Disclosure: The authors have declared that no competing interests existed at the time of publication.×
  • Correspondence to Maximilian Muenke: mamuenke@mail.nih.gov
  • Editor: Larry Humes
    Editor: Larry Humes×
Article Information
Hearing Disorders / Special Populations / Genetic & Congenital Disorders / Review Articles
Review Article   |   June 01, 2014
Hearing Loss in Syndromic Craniosynostoses: Introduction and Consideration of Mechanisms
American Journal of Audiology, June 2014, Vol. 23, 135-141. doi:10.1044/2014_AJA-13-0036
History: Received July 20, 2013 , Revised November 20, 2013 , Accepted November 24, 2013
 
American Journal of Audiology, June 2014, Vol. 23, 135-141. doi:10.1044/2014_AJA-13-0036
History: Received July 20, 2013; Revised November 20, 2013; Accepted November 24, 2013
Web of Science® Times Cited: 4

Purpose There are a number of craniosynostosis syndromes with hearing loss—including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes—that result from mutations in the fibroblast growth factor receptor (FGFR) genes. Studies of FGFRs and their ligands, fibroblast growth factors (FGFs), have revealed clues to the precise contribution of aberrant FGFR signaling to inner ear morphogenesis and the hearing loss encountered in craniosynostoses. The purpose of this article is to review basic studies of FGFRs with emphasis on their function and expression in the inner ear and surrounding structures.

Method A Medline search was performed to find basic science articles regarding FGFR, their ligands, and their expression and relevant mouse models. Additional items searched included clinical descriptions and studies of individuals with FGFR-related craniosynostosis syndromes.

Results The FGF signaling pathway is essential for the morphogensis and proper function of the inner ear and auditory sensory epithelium.

Conclusion The variable auditory phenotypes seen in individuals with Muenke syndrome may have a genetic basis, likely due to multiple interacting factors in the genetic environment or modifying factors. Further analysis and studies of mouse models of Muenke syndrome, in particular, may provide clues to the specific effects of the defining mutation in FGFR3 in the inner ear not only at birth but also into adulthood. In particular, investigations into these models may give insight into the variable expression and incomplete penetrance of this phenotype.

Acknowledgments
This research was supported by the Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health [NIH], Department of Health and Human Services, USA), Protocol No. 05-HG-0131, awarded to the last author. We would like to express our gratitude to the individuals who participate in our ongoing studies of Muenke syndrome at the NIH. We are also grateful to Carmen Brewer of the National Institute on Deafness and Other Communication Disorders for her review of this article.
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