Hearing Impairment in Xeroderma Pigmentosum: Animal Models and Human Studies

Progressive neurological symptoms, including hearing loss, occur in some patients with xeroderma pigmentosum (XP). Patients with neurodegeneration commonly have mutations in XP-A, XP-B, XP-D, XP-F, or XP-G. Typically, audiograms of patients with XP who have sensorineural hearing loss are downsloping. The degree of hearing loss is directly correlated with neurological involvement, including cognitive impairment. Thus, for audiometric assessment, auditory brainstem response (ABR) or other objective tests are sometimes required instead of pure-tone audiometry. In the human temporal bone, XP-mediated pathology includes atrophy of the organ of Corti, stria vascularis, and spiral ganglion neurons. Xpa-deficient mice also showed significant loss of spiral ganglion neurons in the cochlea. Several studies show that the cochlea and nervous system in patients with XP are susceptible to persistent genomic stress, such as reactive oxygen species (ROS), which leads to early onset of sensorineural hearing loss. Regular audiometric monitoring of the hearing status of patients with XP to identify the need for auditory interventions, such as hearing aids, is important for maintaining their quality of life.