Longitudinal and cross-sectional phenotype analysis in a new, large Dutch DFNA2/KCNQ4 family.
We analyzed hearing thresholds, speech recognition scores, and vestibular responses in 32 affected persons in a large family with DFNA2/KCNQ4-related hearing impairment caused by a W276S missense mutation. Linear regression analysis of individual longitudinal data revealed significant threshold progression (1 dB/y) and offset (at age zero). The mean offset thresholds were 5, 21, 40, 39, 31, and 51 dB hearing level (HL) at 0.25, 0.5, 1, 2, 4, and 8 kHz, respectively. Cross-sectional analysis of last-visit thresholds against age produced less-steep slopes and higher offset thresholds. Nonlinear regression analysis of last-visit phoneme recognition scores against age in 25 cases showed that speech recognition did not deteriorate before the third decade. A hyperactive vestibuloocular reflex was found in 3 of 11 cases: 2 persons were especially susceptible to motion sickness. Persons with this KCNQ4 mutation showed congenital, progressive high-frequency impairment without substantial loss of speech recognition during the first decades of life.
De Leenheer
Els M R
EM
Department of Otorhinolaryngology, University Medical Center St Radboud Nijmegen, The Netherlands.
Huygen
Patrick L M
PL
Coucke
Paul J
PJ
Admiraal
Ronald J C
RJ
van Camp
G
G
Cremers
Cor W
CW
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001299:Audiometry; D001309:Auditory Threshold; D002648:Child; D002874:Chromosome Mapping; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D051656:KCNQ Potassium Channels; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D017711:Nonlinear Dynamics; D010375:Pedigree; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D014724:Vestibular Function Tests
D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated