Genotype-phenotype Correlation Study of Presymptomatic and Symptomatic DFNA9 Patients
- Conditions
- Vestibular DiseasesDFNA9
- Registration Number
- NCT03716908
- Lead Sponsor
- Jessa Hospital
- Brief Summary
DFNA9 (Deafness Autosomal Dominant 9) is an autosomal dominant hereditary hearing loss which is associated with vestibular deterioration. The most recent genotype-phenotype correlation studies have been conducted more than 15 years ago. Meanwhile, emerging and valuable vestibular tests have been added to the vestibular test battery. These tests were not available at the time of the correlation studies. The aim of this study is to carry out a prospective cross-sectional study on symptomatic and presymptomatic affected carriers of the Pro51Ser (P51S) Coagulation Factor C Homology (COCH) mutation in order to correlate vestibular data using the complete vestibular test battery with the known data on hearing and vestibular function in relation to age.
- Detailed Description
Systematic review of the genotype-phenotype correlation studies in P51S carriers has shown an underrepresentation of presymptomatic affected subjects and the calculation of vestibular deterioration were based on just one vestibular parameter, whereas the combined evaluation of a complete vestibular test battery, covering the complete vestibular sensitivity range and all labyrinthine compartments separately, is nowadays considered standard practice in determining more accurate assessment of the vestibular function.
For this reason, a prospective cross-sectional study on pre- as well as symptomatic DFNA9 patients carrying the Pro51Ser (P51S) mutation in COCH gene is being carried out, in order to gain more realistic data on vestibular dysfunction, consisting of pure tone audiometry and a comprehensive vestibular test battery, including electro- or videonystagmography (VNG), C- and O-Vestibular-evoked myogenic potential (VEMP) tests, video Head Impulse Test (vHIT) and questionnaires (DHI (Dizziness handicap Index), oscillopsia questionnaire (OS), Quality of Life Questionnaire (EQ-5D-5L), activities-specific balance confidence (ABC) scale.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 70
- subject must be 18 year of older
- subject is a family member of the family pedigree's proband(s) carrying a P51S COCH mutation
- subject is younger than 18 years
- subject is not a family member of the pedigree's proband(s) carrying a P51S
- subject cannot undergo investigations (medical and/or mental reasons)
- subject is not willing to be enrolled into the study
- subject suffers other concomitant middle or inner ear disease
- subject has undergone middle ear or inner ear surgery
- subject suffers other concomitant vestibular disease than DFNA9
- subject has undergone vestibular surgery or other non-invasive vestibular treatment (gentamicin intratympanal injections for example)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method hearing threshold 1 year pure tone audiometry, decibel hearing loss (dB HL)
video HIT 1 year video Head Impulse test, gain (eye movement versus head movement)
- Secondary Outcome Measures
Name Time Method OS questionnaire 1 year A questionnaire assessing oscillopsia severity for patients with bilateral vestibulopathy and patients with unilateral vestibular lesions. Oscillopsia was defined as a "sensation that the visual environment is moving when it's not." The 9-item questionnaire investigates oscillopsia frequency in different situations encountered in daily life. Each item was scored 1 (never), 2 (seldom), 3 (sometimes), 4 (often), or 5 (always). Scores were averaged to provide an oscillopsia severity score ranging from 1 to 5. A mean score higher than 3 is considered to indicate moderate to extreme oscillopsia severity.
SHAT 1 year Sinusoidal harmonic acceleration test (SHAT) of rotatory chair in the dark with open eyes, degrees per second, normative values to be established for each vestibular laboratory on healthy control subjects
EQ-5D-5L questionnaire 1 year Quality of life questionnaire:EQ-5D is a standardised measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal; 5 dimensions: anxiety/depression, discomfort/pain, usual activities, mobility and self-care are evaluated in 5 levels (ranging from no problems (level 1) to extreme problems (level 5) and a Vertical Visual Analogue Scale (VAS) EQ-VAS ranging from 0 (worst health) to 100 (best health), convertible to an index value. result presentation in EQ-5D (dimensions), EQ-VAS and EQ-5D-5L index values with normative values per age group, all as a measure of central tendency and a measure of dispersion using mean values and standard deviation per age group
ABC questionnaire 1 year ABC activities specific balance confidence scale to asses individual's confidence in performing daily activities , scores from 0-100%, normative values \>80%
VEMP 1 year c- and o-VEMP tests (vestibular-evoked myogenic potentials): threshold (decibel sound pressure level: dB SPL or dB HL)
Caloric response 1 year Caloric response using 4 successive water irrigation at 30 and 44 degrees Celsius , summation of the gain of the slow phase of the elicited nystagmus of all 4 irrigations (degrees per second) , normative values to be established for each vestibular laboratory in healthy control subjects
DHI questionnaire 1 year DHI (dizziness handicap index): scores the degree of imbalance perception of the patient, the higher the score, the higher the imbalance perception; normative score below 10
Trial Locations
- Locations (1)
University of Antwerp
🇧🇪Antwerpen, Belgium