Stapes ankylosis in a family with a novel NOG mutation: otologic features of the facioaudiosymphalangism syndrome

Objective: To report the phenotype-genotype correlation in a Belgian family that was ascertained to have a novel missense mutation in the NOG gene mapping to chromosome 17q22.

Study design: To describe the phenotype, a retrospective case study was performed based on the otologic, audiologic, ophthalmologic, and radiologic data of the mutation carriers of the NOG gene.

Setting: Tertiary referral center.

Patients: All members of a Belgian kindred who carried the novel missense mutation in the NOG gene (NOG, Trp205Cys [W205C]; 1426G>C).

Interventions: Diagnostic otologic and ophthalmologic examination, audiometric analysis, and radiologic imaging.

Main outcome measures: Phenotype-genotype correlations.

Results: All five mutation carriers had a typical facies. Bilateral proximal symphalangism and hyperopia were present in 80%. Five of 10 ears also had progressive early-onset conductive hearing loss caused by stapes ankylosis.

Conclusions: So far, 14 independent NOG mutations have been identified. The autosomal dominant disorder described in the present family was caused by a novel NOG missense mutation (NOG, Trp205Cys [W205C]; 1426G>C). The phenotype correlated well with the facioaudiosymphalangism syndrome. The mutation carriers demonstrated progressive multiple joint fusions, hyperopia, early-onset conductive deafness, and a typical facies.