title: Otosclerosis or congenital stapes ankylosis? The diagnostic role of genetic analysis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Emery
authors.forename: Anna
authors.initials: A
authors.lastname: Meyer
authors.forename: Laura
authors.initials: L
authors.lastname: Miller
authors.forename: Marci M
authors.initials: MM
authors.lastname: Lesperance
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000844:Ankylosis / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004427:Ear Diseases / Q000151:congenital* / Q000235:genetics*; D005260:Female; D005385:Fingers / Q000002:abnormalities; D006312:Hearing Loss, Bilateral / Q000209:etiology / Q000503:physiopathology; D006314:Hearing Loss, Conductive / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010040:Otosclerosis / Q000235:genetics*; D010641:Phenotype; D010808:Physical Examination; D013199:Stapes / Q000002:abnormalities* / Q000473:pathology; D013577:Syndrome; D013580:Synostosis / Q000473:pathology; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D004247:DNA; D000099176:Noggin Protein