Temporal Bone Histopathology in NOG-Symphalangism Spectrum Disorder

To describe the human temporal bone histopathology in NOG-related symphalangism spectrum disorder, a spectrum of congenital stape fixation syndromes caused by mutations in the NOG gene. To discuss implications for clinical management.

A patient with a mutation in the NOG gene.

Removal of temporal bones, postmortem temporal bone computed tomography, histologic processing, and review of temporal bones.

Temporal bone histopathology and correlation with clinical, genetic, audiologic, and radiologic evaluations.

Both temporal bones demonstrated fixation of the stapes footplate to the otic capsule because of a circumferential bridge of calcified cartilage. In the right ear (unoperated), there was no additional abnormality of the ossicles or ossicular joints. In the left ear, fenestrations of the stapes footplate and the lateral semicircular canal were seen, consistent with a history of stapedectomy and fenestration procedure. Severe loss of spiral ganglion neurons throughout the left cochlea accounted for the profound sensorineural hearing loss; there was a normal number of spiral ganglion neurons in the right ear. In both ears, the cochleae demonstrated grossly preserved organs of Corti.

The temporal bone pathologic correlate for conductive hearing loss in this patient with a NOG mutation was circumferentially calcified cartilage bridging the stapedovestibular joint space. The temporal bone histopathology findings suggest that conductive hearing loss related to NOG mutation should be improved after stapedectomy; however, care must be taken in extrapolating to all patients with NOG mutations because there may be variability in the pathology, especially given the variability of NOG spectrum disorders.