Clinical evidence for dystrophin dysfunction as a cause of hearing loss in locus DFN4.

Objective: Locus DFN4 is an X-linked nonsyndromic hearing loss locus originally mapped to Xp21.2. Recently, we have mapped deafness in a second family from Turkey to the same region, refining the location to within the Duchenne muscular dystrophy (DMD) locus. The objective of this study was to characterize the clinical phenotype of the Turkish family with comprehensive audiovestibular testing and high-resolution temporal bone computerized tomography.

Methods: Fourteen members of a three-generation family were studied in detail including two deaf affected males. Members of the family underwent general physical and otologic examination, vestibular testing, pure-tone audiometry, otoacoustic emissions, and immitance testing. An affected male underwent high-resolution computerized tomography of the temporal bone, electroretinogram (ERG), electromyography, electroneurography, and determination of serum creatinine phosphokinase level.

Results: Affected males were congenitally deaf with normal vestibular function. Carrier females showed a mild sensorineural hearing loss affecting all frequencies and absent otoacoustic emissions. Otoacoustic emissions in a younger, 3-year-old carrier girl were normal. In an affected male, ERG demonstrated subnormal scotopic b-wave typically seen in DMD. Computerized tomography of the temporal bone was normal. With the exception of the ERG finding, there was no clinical or laboratory evidence of DMD or Becker muscular dystrophy (BMD).

Conclusion: The abnormal ERG in the Turkish family in conjunction with mapping of the DFN4 locus to within DMD strongly suggests that a defect in dystrophin is responsible for the hearing loss in this family. Patients with DMD and BMD should be screened systematically for sensorineural hearing loss. This family provides additional evidence for the critical role of cytoskeletal proteins in normal hearing.