Our central hypothesis that adults with type I OI display signs of otosclerosis and infants who died from type II OI display abnormalities of endochondral ossification was supported by the histologic findings among the nine cases we identified. All four adults with OI had histologic evidence of otosclerosis. This was also observed in a 9 year old child with type III OI. The four infants with type II OI had decreased endochondral ossification compared with age matched controls. We hypothesize that in adults abnormal type I collagen results in increased bony turnover in the otic capsule which ultimately results in the development of otosclerosis. Further investigation is warranted to evaluate the cause of the variability observed in the location of otosclerotic foci in OI.
The reported prevalence of hearing loss in OI approximates 50% (2
). Hearing loss occurs in conductive, sensorineural, and mixed patterns. A recent clinical study of 41 adult type I OI patients with COL1A1 and COL1A2 mutations found no correlation between genotype and auditory phenotype. Moreover, there was no intra-familial correlation to the pattern of hearing loss (3
). This observation has been replicated in other studies, where a genotype-auditory phenotype correlate and an association with other risk factors for hearing loss – including otitis media, skull fracture and noise exposure – were not identified (4
In the current study, there was limited availability of clinical audiometric data. Among the four adult type I OI patients, three had clinically confirmed hearing loss or histologic evidence to suggest clinically relevant hearing loss. One patient had a documented mixed hearing loss, one patient had documented sensorineural hearing loss, and one patient did not have an available audiogram but histopathology revealed an obliterated footplate indicating at minimum a conductive hearing loss. There was no history or histopathologic correlate of hearing loss in the other patient. All adults with type I OI had histologic evidence of otosclerosis. The presentation of otosclerotic lesions included patterns of histologic otosclerosis (a lesion without fixation of the footplate or known hearing loss – cases 1and 3), clinical otosclerosis (fixation of the footplate with conductive hearing loss – case 2 and 4) and cochlear otosclerosis (sensorineural hearing loss without stapes fixation where hyalinization of the stria vascularis is thought to induce sensorineural hearing loss (12
)– case 4). Separation of the stapes supra-structure from a fixed footplate (case 2) was also observed and would result in a conductive hearing loss. This may have resulted from bony fracture or atrophy.
These histopathologic findings highlight three potential etiologies of clinically relevant hearing loss in osteogenesis imperfecta. The first includes otosclerosis mediated conductive, mixed and sensorineural hearing loss. The second mechanism is fracture or atrophy of the stapes. This fracture or atrophy could be related to osteogenesis imperfecta through weakened bone and fixation of the stapes from otosclerosis or could potentially develop from abnormal bone turnover. A third mechanism, primary neural degeneration, was raised by one case (case 3). COL1A2 is expressed in moderate to high levels in membranous cochlear cells (13
) the function of which remains unknown. Dismorphic collagen expression within the cochlea could be responsible for the neural degeneration noted.
The otopathology of OI has important implications for the treating otologic surgeon. Adult patients with type I OI and conductive or mixed hearing loss likely have clinical otosclerosis. For those that elect to undergo stapedotomy, the surgeon must evaluate the status of the round window because it may be obliterated due to otosclerosis in OI and round window obliteration may be responsible for failure of hearing improvement following stapedotomy. Patients with profound hearing loss may be candidates for cochlear implantation. Cavitary otosclerotic lesions are seen in OI and could represent an avenue for electrode misplacement. Pre-operative CT imaging may demonstrate these lesions and highlight patients at risk of this complication.