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Otosclerosis or Congenital Stapes Ankylosis? The Diagnostic Role of Genetic Analysis

Emery, Sarah B.; Meyer, Anna; Miller, Laura; Lesperance, Marci M.

doi: 10.1097/MAO.0b013e31819e6398
Basic Science

Hypothesis: Molecular genetic testing is useful to differentiate otosclerosis from syndromic stapes ankylosis.

Background: Congenital stapes ankylosis is genetically heterogeneous. Mutations in the NOG gene are known to be associated with a variety of rare stapes ankylosis syndromes including stapes ankylosis with broad thumbs and toes, multiple synostoses syndrome, and proximal symphalangism. These syndromes have overlapping clinical features that may be unrecognized.

Methods: The proband was a 54-year-old woman diagnosed in childhood with bilateral maximal conductive hearing loss. Audiologic, medical, and surgical records were reviewed. Deoxyribonucleic acid (DNA) was obtained from peripheral lymphocytes. DNA sequencing was used to assay for mutations in the NOG gene.

Results: Clinical genetics evaluation was most consistent with proximal symphalangism, but features of multiple synostoses syndrome were identified as well. DNA sequencing revealed a heterozygous p.W205C mutation in the NOG gene, not found in 100 controls.

Conclusion: Evaluation of the patient with stapes ankylosis should include a family history and specific inquiry into features associated with stapes ankylosis syndromes, such as bony anomalies of the spine, hands, and feet. However, a negative family history does not exclude the possibility of a syndrome. Many patients who are thought to have nonsyndromic otosclerosis actually have syndromes caused by mutations in the NOG gene. Identifying a syndrome has implications for surgical management and prognosis.

Division of Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan, U.S.A.

Address correspondence and reprint requests to Marci M. Lesperance, M.D., F6866 Mott SPC 5241, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-5241; E-mail:

This work was supported by a Translational Research Award from the Biomedical Research Council at the University of Michigan Medical School.

Presented at the Politzer Society's 2nd Symposium on Otosclerosis and Stapes Surgery in Biarritz, France, on May 8, 2008.

© 2009 Otology & Neurotology, Inc.