Bi-allelic inactivating variants in the COCH gene cause autosomal recessive prelingual hearing impairment.

Pathogenic variant in COCH are a known cause of DFNA9 autosomal dominant progressive hearing loss and vestibular dysfunction with adult onset. Hitherto, only dominant nonsynonymous variants and in-frame deletions with a presumed dominant negative or gain-of-function effect have been described. Here, we describe two brothers with congenital prelingual deafness and a homozygous nonsense c.292C>T(p.Arg98*) COCH variant, suggesting a loss-of-function effect. Vestibular dysfunction starting in the first decade was observed in the older patient. The heterozygous parents and sibling have normal hearing and vestibular function, except for the mother, who shows vestibular hyporeflexia and abnormal smooth pursuit tests, most likely due to concomitant disease. This is the first report of autosomal recessive inheritance of cochlea-vestibular dysfunction caused by a pathogenic variant in the COCH gene. An earlier onset of hearing impairment and vestibular dysfunction compared to the dominant hearing loss causing COCH variants is observed.

Focal sclerosis of semicircular canals with severe DFNA9 hearing impairment caused by a P51S COCH-mutation: is there a link?

HYPOTHESIS: Focal sclerosis of one or more semicircular canals on computed tomographic (CT) scans and a corresponding signal loss on magnetic resonance (MR) imaging are radiologic lesions that are linked to patients who are suffering from advanced otovestibular impairment caused by hereditary DFNA9 hearing loss. BACKGROUND: DFNA9 is a hereditary hearing loss that is characterized by late-onset progressive imbalance and hearing deterioration, caused by mutations in the COCH gene. To date, no radiologic lesions have been associated with this condition. STUDY DESIGN: A retrospective chart review SETTING: Tertiary referral center SUBJECTS: The radiologic data of 9 patients who presented between 2007 and 2012 with otovestibular deterioration caused by a mutation in the COCH gene were reviewed. RESULTS: All 9 subjects were carriers of the same c.151C > T, p.Pro51Ser (P51S) - missense mutation in the COCH gene. In 8 of them similar sclerotic lesions and/or narrowing were demonstrated in one or more semicircular canals on computed tomography CT scan, with a signal loss at corresponding areas on T2-weighted magnetic resonance (MR) images. In 1 patient, the posterior part of the vestibule was also affected. The posterior canals were affected in most cases (58%), compared with the superior (21%) and lateral canals (16%) or the vestibule (5%). Only 68.4% of the lesions on MR images were also visible on CT scans, suggesting a fibrotic process without calcification. Ears presenting radiologic lesions showed significantly more severe hearing loss (median PTA 104 dB HL) compared with unaffected ears (58 dB HL). CONCLUSION: Eight of 9 subjects with the same P51S mutation in the COCH gene showed similar radiologic lesions, affecting the PSCC in the majority of the cases. These radiologic abnormalities occurred in more advanced stages of the otovestibular deterioration, supporting the hypothesis that these lesions might represent the end phase of a low-grade chronic inflammation or protein deposition. A new phenotypic and characteristic radiologic feature of DFNA9 has been discovered.

Results, hearing rehabilitation, and follow-up with magnetic resonance imaging after tympanomastoid exenteration, obliteration, and external canal overclosure for severe chronic otitis media.

OBJECTIVES: We sought to evaluate the results, auditory rehabilitation, and follow-up with magnetic resonance imaging (MRI) after tympanomastoid exenteration with obliteration of the mastoid cavity and overclosure of the external ear canal in patients with severe chronic otitis media that was resistant to medical therapy and conventional surgery and was associated with a profound sensorineural or severe conductive hearing loss. METHODS: Twenty-nine patients were analyzed and underwent this surgical technique. Twelve patients had, during the same or later stage, either cochlear implantation, fixture implantation for a bone-anchored hearing aid, or middle ear implantation. For follow-up control of the obliterated cavity, delayed gadolinium-enhanced, T1-weighted MRI in combination with non-echo planar imaging diffusion weighted sequences were used. RESULTS: No patient had recurrent otorrhea after an average follow-up period of 4.75 years. One patient had a residual cholesteatoma as shown by new MRI techniques, and this was successfully resected. One patient developed complications 6 months after 1-stage tympanomastoid exenteration and cochlear implantation. CONCLUSIONS: This technique is very useful in selected patients with severe chronic otitis media that is resistant to medical therapy and surgery and is associated with a profound sensorineural or severe conductive hearing loss. New sequences in MRI are used for postoperative follow-up of these obliterated cavities and seem reliable for the detection of residual or recurrent cholesteatoma. Middle ear implantation and cochlear implantation can be relatively safely performed in these patients in a second stage.