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

Completed

• Conditions: Congenital Profound Hearing Loss

• Registration Number: NCT04202185
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2019-12-16
• Study First Submitted QC: 2019-12-16
• Study First Posted: 2019-12-17
• Study Start: 2020-04-02
• Primary Completion: 2023-10-22
• Study Completion: 2024-12-06
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Prevalence of deafness caused by DFNB9	3 months	Prevalence and type of bi-allelic pathogenic changes Otoferlin Molecular analysis will be done by Next Generation Sequencing Capture method

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Unité d'Audiophonologie et d'Implantation cochléaire - Necker hospital; 🇫🇷 Paris, France