Longitudinal and cross-sectional phenotype analysis in a new, large Dutch DFNA2/KCNQ4 family

Ann Otol Rhinol Laryngol. 2002 Mar;111(3 Pt 1):267-74. doi: 10.1177/000348940211100312.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Aged
  • Audiometry
  • Auditory Threshold
  • Child
  • Chromosome Mapping
  • Cross-Sectional Studies
  • DNA Mutational Analysis*
  • Disease Progression
  • Female
  • Genetic Linkage
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / epidemiology*
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / physiopathology
  • Humans
  • KCNQ Potassium Channels
  • Linear Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation, Missense / genetics
  • Netherlands / epidemiology
  • Nonlinear Dynamics
  • Pedigree
  • Phenotype
  • Potassium Channels / genetics*
  • Potassium Channels, Voltage-Gated*
  • Vestibular Function Tests

Substances

  • KCNQ Potassium Channels
  • KCNQ4 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated