Audiometric characterization of a family with digenic autosomal, dominant, progressive sensorineural hearing loss.

In this study, a non-syndromic progressive bilateral high frequency hearing loss is described in a family with 141 identified members. Recent genetic analyses indicated a digenic inheritance with linkage to the gene loci DFNA2 and DFNA12. The affected family members who shared haplotypes at both loci (type I) showed an early postlingual onset and a more rapid rate of progress compared with those with one either of the two disease associated haplotypes (type II). The audiometric pattern was cochlear without a vestibular involvement. Auditory brainstem response audiometry and magnetic resonance imaging indicated normal retrocochlear features. The otoacoustic emissions were affected for both type I and type II, whereas the acoustic stapedius reflex thresholds were normal in most cases. It is concluded that both types had an outer hair cell/micro-mechanical abnormality, but that the DFNA 2 type might have an additional dysfunction at the level of the inner hair cells. It is furthermore pointed out that the application of refined audiometric techniques as well as a further development of new techniques is needed in order to characterize the phenotypes of the rapidly expanding number of genetically defined inner ear abnormalities.