Focal Sclerosis of Semicircular Canals With Severe DFNA9 Hearing Impairment Caused by a P51S COCH-Mutation

Varebeke, Sebastien Pierre Janssens de; Termote, B; Camp, Guy Van; Govaerts, Paul; Schepers, Steven; Cox, Tony; Deben, Kristof; Ketelslagers, Katrien; Souverijns, Geert

doi:10.1097/mao.0000000000000283

Cited by 25 publications

(38 citation statements)

References 16 publications

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“…The hearing losses are sensorineural. Note the downsloping character of the thresholds Complete physical, serologic, hematologic, urinary, cardiac, renal and ophthalmologic examinations were unremarkable for both brothers and proband's AI-010 Computed tomography (CT) and magnetic resonance imaging (MR) did not show any typical focal sclerotic lesions in any of the semicircular canals similar described in COCH c.151 C>T (P. Pro51Ser) positive patients [9]. Videonystagmography (VNG) showed bilateral symmetrical, but marked hyporeflective caloric response with normal, albeit high amplitudes on pendular chair responses in proband AI-010.…”

Section: Case Detailsmentioning

confidence: 73%

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

et al. 2018

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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.

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Section: Case Detailsmentioning

confidence: 73%

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

et al. 2018

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“…During the last decades, many genotype-phenotype observational reports with auditory and vestibular testing have shown limited variability across subjects and helped to characterize DFNA9 (5,13,14). Recently, JanssensdeVarebeke et al described a correlation between hearing loss and radiological abnormalities in patients with DFNA9, specifically with a P15S mutation in the COCH gene (9). This study suggested that radiological findings and the degree of hearing loss are both linked to the stage of this hereditary disease (9).…”

Section: Discussionmentioning

confidence: 90%

“…This loss of fibrocytes leading to accumulation of acellular substance that probably consists of misfolded COCH protein may be the cause of cytotoxicity (6)(7)(8). Radiologic abnormalities on computed tomography (CT), including narrowing or sclerosis of the SCC, and T2-weighted magnetic resonance imaging (MRI), including signal loss in the SCC, have already been reported as a biomarker in carriers of the P51S mutations in the COCH gene (9). The authors have shown a correlation of these lesions with advanced stages of sensorineural hearing loss, suggesting these lesions to be secondary to an advanced inflammatory process.…”

Section: Introductionmentioning

confidence: 99%

Correlations Between Vestibular Function and Imaging of the Semicircular Canals in DFNA9 Patients

et al. 2020

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Background and Purpose: Radiologic abnormalities on computed tomography (CT), including narrowing or sclerosis of the semicircular canals (SCCs), and T2-weighted magnetic resonance imaging (MRI), including signal loss in the SCC, have been reported as potential biomarkers in patients with P51S mutations in the COCH gene (i.e., DFNA9). The aim of our study was to correlate caloric responses through electronystagmography (ENG) data with imaging results in DFNA9 patients. Materials and Methods: A retrospective study was performed in 45 patients; therefore, 90 ears with P51S mutations in the COCH gene were tested. Caloric responses and CT and MRI data were analyzed from June 2003 until May 2014. More than half of patients (54%) were candidates for cochlear implantation. Results: In our population, 91% of tested ears had sclerotic lesions and/or narrowing in one or more SCCs on CT scan. All tested ears had narrowing or signal loss in at least one SCC on T2-weighted MRI. The lateral SCC was affected in 87% on CT scan and 92% on MRI. However, in 83% of tested ears, all three SCCs were affected on MRI. Furthermore, in 77% of tested ears, caloric responses were reduced bilaterally, while 11.5% showed unilateral hypofunction and the other 11.5% had normal caloric responses. CT abnormalities correlated with hypofunction of caloric responses. This statistically significant difference was present if abnormalities were observed in at least one of the SCCs as well as in ipsilateral lateral SCC function loss. MRI abnormalities in at least one of the SCCs correlated with ENG hypofunction, but there was no direct correlation between lateral SCC abnormalities on MRI and caloric responses of the investigated lateral canal. Conclusion: Our retrospective analysis confirms the presence of CT and MRI abnormalities in DFNA9 patients with the P51S mutation in the COCH gene. A correlation between these radiologic features and vestibular function (tested by means of caloric response) was found in this population.

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“…At the best of our knowledge there are no studies that have already investigated MR findings of DFNA9 ears by a 3 Tesla scanner and using pre-and postcontrast 3D-FLAIR sequences, which has been demonstrated to be an emerging technique able to add new insights about different inner ear pathologies, such as sudden hearing loss and Ménière's disease [Conte et al, 2017]. Another study had attempted to assess the morphology of DFNA9 ears by computed tomography and by MRI using classic heavily-T2 MR sequence, which is, unfortunately, less sensitive in detecting the changes in inner ear structures [De Varebeke et al, 2014].…”

Section: Discussionmentioning

confidence: 99%

Audiovestibular Phenotypes and Advanced Magnetic Resonance Imaging Features of Cochlin Gene Mutation Carriers

et al. 2019

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Objective: to describe clinical and imaging findings in a group of patients affected by non-syndromic deafness A9 (DFNA9), using advanced Magnetic Resonance (MR) imaging with three-dimensional (3D) Fluid-Attenuated Inversion Recovery (FLAIR) sequence.Method: a retrospective case review was conducted in a tertiary referral center in Italy. Four sequential adult DFNA9-affected patients, who had undergone MR imaging at our Department between January 2017 and June 2018, were enrolled (Male = 2, Female = 2; median age: 65,6yr; 8 diseased ears analyzed). Three patients were relatives; the fourth was unrelated. The main outcome measures -age, sex, records of audiological and vestibular testing, genetic assessment, MR imaging findings -were analyzed.Results: All subjects suffered from bilateral progressive sensorineural hearing loss, more severe on the high frequencies and typical clinical pattern of bilateral chronic degenerative cochleo-vestibular deficit. Aural fullness was reported at the onset of the disease. All patient revealed a pathogenic heterozygous mutation in the Limulus factor C, Coch-5b2 and Lgl1 domain (LCCL) of cochlin. None of the patients showed a significant vestibular and cochlear endolymphatic hydrops at MR imaging, while high bilateral contrast enhancement on 4hs-delayed postcontrast 3D-FLAIR sequence was observed in all ears.Conclusions: increased perilymph enhancement on 4hs-delayed postcontrast 3D-FLAIR sequence is the common imaging feature of DFNA9 ears, suggesting that blood-labyrinthine barrier (BLB) breakdown may play the main role in the pathophysiology of this disease. Significant hydrops has been excluded by MR imaging. This finding might be clinically useful in differentiating DFNA9 disease from other pathologies with similar clinical findings like Ménière's disease.

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Focal Sclerosis of Semicircular Canals With Severe DFNA9 Hearing Impairment Caused by a P51S COCH-Mutation

Cited by 25 publications

References 16 publications

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

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

Correlations Between Vestibular Function and Imaging of the Semicircular Canals in DFNA9 Patients

Audiovestibular Phenotypes and Advanced Magnetic Resonance Imaging Features of Cochlin Gene Mutation Carriers

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