Evaluation of a Cohort of Congenital Deep Deafness Patients and/or With Auditory Neuropathy, Looking for DFNB9

Study Overview
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Brief Summary
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Evaluation of a cohort of deaf children looking for autosomal recessive deafness-9 (DFNB9). Clinical and audiologic evaluation of patients with known auditive neuropathy / auditory dys-synchrony (ANAD) or recently diagnosed congenital severe to profound hearing loss (HL), and assessing genetic analysis looking for DFNB9. The investigators expect to compile genotypic and phenotypic characterization of 25 children with DFNB9 within 4 years.

Detailed Description
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ANAD is not a rare type of hearing loss. Nevertheless, its profile is heterogeneous and the pathology remain underdiagnosed. The investigators will screen all new patients with bilateral severe to profound HL, looking for DFNB9. They will analyse their electrophysiology (auditory potential, and otoacoustic emission), and their audio-vestibular profile, at an early stage and one year after inclusion. All patients will be seen in the genetic clinic. Also, the investigators will analyse all patients with ANAD profile and patients known with ANAD. All informations will provide precise data base to allow a better understanding of the pathology. It might also lead to select the best candidates for future gene therapy

Official Title
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Evaluation of a Cohort of Congenital Deep Deafness Patients and/or With Auditory Neuropathy, Looking for DFNB9

Conditions
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Congenital Profound Hearing Loss

Intervention / Treatment
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* Other: Data collection
* Genetic: Genetic analysis


Participation Criteria
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Eligibility Criteria
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G1a / Inclusion Criteria: Child from 0 to 3 years old Child with severe to profound bilateral deafness newly diagnosed with: Average hearing threshold> 70 decibel on each ear and / or no response to 70 decibel PEA on each ear and / or no response to ASSR G1b / Inclusion Criteria: Child under 16 Child with newly diagnosed hearing neuropathy : tonal/vocal dissociation (when this is possible), and/or modified PEA, and/or discordant ASSR, and/or OEA present. G2 / Inclusion Criteria: Adult patient under 25 or child Patient with deafness with auditory neuropathy Patient known to have 1 or 2 mutations of the otoferlin protein Exclusion Criteria: Other type of deafness such as : unilateral deafness, deafness of transmission, malformation syndrome, known genetic familial deafness not DFNB9 Patient without medical insurance Lack of consent to DNA sampling, of one or both biological parents (consent of the care)

Ages Eligible for Study
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Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| G1a<br>infants under 3 years deaf severe to deep | Other: Data collection<br>* Retrospective collection data from diagnostic Data collected following to medical exam as part of care<br>Genetic: Genetic analysis<br>* Research of mutation and identification of genetic panel as part of care<br>|
| G1b<br>children under 16 years of age with audiologically proven auditory neuropathy | Other: Data collection<br>* Retrospective collection data from diagnostic Data collected following to medical exam as part of care<br>Genetic: Genetic analysis<br>* Research of mutation and identification of genetic panel as part of care<br>|
| G2<br>patients <25 years old with one or two Otoferlin mutations | Other: Data collection<br>* Retrospective collection data from diagnostic Data collected following to medical exam as part of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of deafness caused by DFNB9 | Prevalence and type of bi-allelic pathogenic changes Otoferlin Molecular analysis will be done by Next Generation Sequencing Capture method | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Audiological characteristics in free fields at diagnosis | audiometric thresholds on 500, 1000, 2000, 4000 Hz in free fields | 1 day | 
| Audiological characteristics in separate ears at diagnosis | audiometric thresholds on 500, 1000, 2000, 4000 Hz in separate ears | 1 day | 
| Audiological characteristics in free fields at 12 months or last record | audiometric thresholds on 500, 1000, 2000, 4000 Hz in free fields | 12 months | 
| Audiological characteristics in separate ears at 12 months or last record | audiometric thresholds on 500, 1000, 2000, 4000 Hz in separate ears | 12 months | 
| Electrophysiological characteristics : auditory evoked potentials (PEA) at diagnosis | PEA thresholds per ear | 1 day | 
| Electrophysiological characteristics : auditory evoked potentials (PEA) at 12 months or last record | PEA thresholds per ear | 12 months | 
| Electrophysiological characteristics : auditory Steady State Response (ASSR) at diagnosis | ASSR thresholds per ear at 500, 1000, 2000, 4000 Hz | 1 day | 
| Electrophysiological characteristics : auditory Steady State Response (ASSR) at 12 months or last record | ASSR thresholds per ear at 500, 1000, 2000, 4000 Hz | 12 months | 
| Electrophysiological characteristics : otoacoustic emissions (OEAs) at diagnosis | OEAs status | 1 day | 
| Electrophysiological characteristics : otoacoustic emissions (OEAs) at 12 months or last record | OEAs status | 12 months | 
| Vestibular characteristics : per-oral endoscopic myotomy (PEOM) at diagnosis | PEOM | 1 day | 
| Vestibular characteristics : per-oral endoscopic myotomy (PEOM) at 12 months or last record | PEOM | 12 months | 
| Vestibular characteristics : video Head Impulse Test (VHIT) at diagnosis | VHIT | 1 day | 
| Vestibular characteristics : video Head Impulse Test (VHIT) at 12 months or last record | VHIT | 12 months | 
| Caloric Tests at diagnosis | Caloric Tests | 1 day | 
| Caloric Tests at 12 months or last record | Caloric Tests | 12 months | 
| Clinical development scale at diagnosis | For child under 3 years with : walk age, sitting age and head held age | 1 day | 
| Clinical development scale at 12 months or last record | For child under 3 years with : walk age, sitting age and head held age | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Auditory neuropathy, DFNB9, Children, Hearing loss, Deafness