Clinical trial NCT04202185: Evaluation of a Cohort of Congenital Deep Deafness Patients And/or with Auditory Neuropathy, Looking for DFNB9
Official title: Evaluation of a Cohort of Congenital Deep Deafness Patients And/or with Auditory Neuropathy, Looking for DFNB9
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Profound Hearing Loss
Keywords: Auditory neuropathy
DFNB9
Children
Hearing loss
Deafness
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-12-17
Enrollment: 150
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient coming to the Necker Hospital for a deafness visit or for a check-up prior to a cochlear implantation

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

Eligibility criteria: 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)

Primary outcomes:
measure: Prevalence of deafness caused by DFNB9
timeFrame: 3 months
Secondary outcomes:
measure: Audiological characteristics in free fields at diagnosis
timeFrame: 1 day
measure: Audiological characteristics in separate ears at diagnosis
timeFrame: 1 day
measure: Audiological characteristics in free fields at 12 months or last record
timeFrame: 12 months
measure: Audiological characteristics in separate ears at 12 months or last record
timeFrame: 12 months
measure: Electrophysiological characteristics : auditory evoked potentials (PEA) at diagnosis
timeFrame: 1 day
measure: Electrophysiological characteristics : auditory evoked potentials (PEA) at 12 months or last record
timeFrame: 12 months
measure: Electrophysiological characteristics : auditory Steady State Response (ASSR) at diagnosis
timeFrame: 1 day
measure: Electrophysiological characteristics : auditory Steady State Response (ASSR) at 12 months or last record
timeFrame: 12 months
measure: Electrophysiological characteristics : otoacoustic emissions (OEAs) at diagnosis
timeFrame: 1 day
measure: Electrophysiological characteristics : otoacoustic emissions (OEAs) at 12 months or last record
timeFrame: 12 months
measure: Vestibular characteristics : per-oral endoscopic myotomy (PEOM) at diagnosis
timeFrame: 1 day
measure: Vestibular characteristics : per-oral endoscopic myotomy (PEOM) at 12 months or last record
timeFrame: 12 months
measure: Vestibular characteristics : video Head Impulse Test (VHIT) at diagnosis
timeFrame: 1 day
measure: Vestibular characteristics : video Head Impulse Test (VHIT) at 12 months or last record
timeFrame: 12 months
measure: Caloric Tests at diagnosis
timeFrame: 1 day
measure: Caloric Tests at 12 months or last record
timeFrame: 12 months
measure: Clinical development scale at diagnosis
timeFrame: 1 day
measure: Clinical development scale at 12 months or last record
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Unité d'Audiophonologie et d'Implantation cochléaire - Necker hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Nathalie LOUNDON, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Denoyelle F, Petit C. DFNB9. Adv Otorhinolaryngol. 2002;61:142-4. doi: 10.1159/000066822. No abstract available.
citation: Loundon N, Marcolla A, Roux I, Rouillon I, Denoyelle F, Feldmann D, Marlin S, Garabedian EN. Auditory neuropathy or endocochlear hearing loss? Otol Neurotol. 2005 Jul;26(4):748-54. doi: 10.1097/01.mao.0000169044.63970.4a.
citation: Marlin S, Feldmann D, Nguyen Y, Rouillon I, Loundon N, Jonard L, Bonnet C, Couderc R, Garabedian EN, Petit C, Denoyelle F. Temperature-sensitive auditory neuropathy associated with an otoferlin mutation: Deafening fever! Biochem Biophys Res Commun. 2010 Apr 9;394(3):737-42. doi: 10.1016/j.bbrc.2010.03.062. Epub 2010 Mar 16.
citation: Mehl AL, Thomson V. The Colorado newborn hearing screening project, 1992-1999: on the threshold of effective population-based universal newborn hearing screening. Pediatrics. 2002 Jan;109(1):E7. doi: 10.1542/peds.109.1.e7.
citation: Migliosi V, Modamio-Hoybjor S, Moreno-Pelayo MA, Rodriguez-Ballesteros M, Villamar M, Telleria D, Menendez I, Moreno F, Del Castillo I. Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss. J Med Genet. 2002 Jul;39(7):502-6. doi: 10.1136/jmg.39.7.502. No abstract available.
citation: Rouillon I, Marcolla A, Roux I, Marlin S, Feldmann D, Couderc R, Jonard L, Petit C, Denoyelle F, Garabedian EN, Loundon N. Results of cochlear implantation in two children with mutations in the OTOF gene. Int J Pediatr Otorhinolaryngol. 2006 Apr;70(4):689-96. doi: 10.1016/j.ijporl.2005.09.006. Epub 2005 Oct 13.
citation: Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Bahloul A, Perfettini I, Le Gall M, Rostaing P, Hamard G, Triller A, Avan P, Moser T, Petit C. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell. 2006 Oct 20;127(2):277-89. doi: 10.1016/j.cell.2006.08.040.
citation: Varga R, Avenarius MR, Kelley PM, Keats BJ, Berlin CI, Hood LJ, Morlet TG, Brashears SM, Starr A, Cohn ES, Smith RJ, Kimberling WJ. OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. J Med Genet. 2006 Jul;43(7):576-81. doi: 10.1136/jmg.2005.038612. Epub 2005 Dec 21.
citation: Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet. 1999 Apr;21(4):363-9. doi: 10.1038/7693.