Otologic and audiologic manifestations of hutchinson-gilford progeria syndrome

Authors

  • Elizabeth Guardiani MD,

    1. Georgetown University Hospital Department of Otolaryngology–Head and Neck Surgery, Washington, DC
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  • Christopher Zalewski MA,

    1. National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland
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  • Carmen Brewer PhD,

    1. National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland
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  • Melissa Merideth MD, MPH,

    1. Office of the Clinical Director, National Human Genome Research Institute, Bethesda, Maryland
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  • Wendy Introne MD,

    1. Office of the Clinical Director, National Human Genome Research Institute, Bethesda, Maryland
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  • Ann C. M. Smith MA, DSc(Hon),

    1. Office of the Clinical Director, National Human Genome Research Institute, Bethesda, Maryland
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  • Leslie Gordon MD, PhD,

    1. Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island
    2. Department of Anesthesia, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, U.S.A
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  • William Gahl MD, PhD,

    1. Office of the Clinical Director, National Human Genome Research Institute, Bethesda, Maryland
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  • H. Jeffrey Kim MD

    Corresponding author
    1. Georgetown University Hospital Department of Otolaryngology–Head and Neck Surgery, Washington, DC
    2. National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland
    • Department of Otolaryngology–Head and Neck Surgery, 1st Floor Gorman Building, 3800 Reservoir Road NW, Washington, DC 20007
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  • This work was supported by the intramural research programs of the National Human Genome Research Institute and the National Institute on Deafness and Other Communication Disorders. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

  • Presented in part at the Triological Society Annual Meeting, Las Vegas, Nevada, April 30 – May 1, 2010.

Abstract

Objectives/Hypothesis:

To define the audiologic and otologic phenotype of Hutchinson-Gilford progeria syndrome (HGPS).

Study Design:

Prospective case series.

Methods:

Fifteen patients with HGPS were enrolled in a prospective natural history study; 14 were evaluated in the neurotology clinic, and 11 received audiologic evaluations. The physical exam and audiologic findings of these patients were reviewed to define an otologic and audiologic phenotype for HGPS in the largest series of subjects in the literature.

Results:

All patients were noted to have stiff auricular cartilages, small or absent lobules, and hypoplasia of the lateral soft-tissue portion of the external ear canal leading to a shortened canal. Ten of 14 patients (71%) had dry cerumen impaction, and four of 14 patients (29%) reported a history of recurrent otitis media. Nineteen of 22 ears (86.4%) demonstrated low-frequency conductive hearing loss in the 250 to 500 Hz range. Sixteen of 22 ears (73%) had type A tympanograms; three of 22 ears (14%) displayed bimodal or “W” peaked tympanograms; two of 22 ears (9%) had type B tympanograms; one of 22 ears (4%) had a type C tympanogram. Nine of 10 patients had distortion product otoacoustic emissions consistent with normal peripheral hearing sensitivity.

Conclusions:

HGPS is caused by a mutation in the LMNA gene resulting in the production of an abnormal nuclear protein; this in turn affects nuclear structure and function. Patients with HGPS have characteristic otologic features due to cartilaginous and subcutaneous tissue abnormalities and typically demonstrate low-frequency conductive hearing loss despite largely normal tympanometry. It is important to be aware of these conditions in managing these patients.

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