Abstract
Although hearing impairment is often listed as a nonskeletal complication of X-linked hypophosphatemia (XLH), the prevalence, etiology, pathology, and natural history are poorly described. This review aims to summarize existing literature with a view to guide the clinical management of hearing impairment in XLH. The review was conducted by 2 researchers independently. Four databases (PubMed/Medline, EMBASE, Web of Science, and Cochrane Library) were searched between January 1, 2000 and July 31, 2024, with keywords related to "X-linked hypophosphataemic rickets" and "hearing loss" including synonyms. Identified records were screened for inclusion and exclusion criteria. Human and animal studies were included. Out of 82 records found excluding duplicates, 12 studies met the final criteria and were reviewed. Studies described both conductive and sensorineural hearing loss in 13%-76% of adults with XLH, with sensorineural hearing loss more commonly reported, with impairment developing in adulthood, affecting high and low frequencies, and may be fluctuating. Evidence suggests that endolymphatic hydrops (ELH) may be a major underlying cause of hearing loss in XLH. Individuals with XLH have generalized osteosclerosis with petrous bone thickening and narrowing of the auditory meatus. No studies have looked at burosumab, a monoclonal antibody that inhibits FGF23, and its effect on the development of hearing loss in individuals with XLH. Animal studies of XLH mouse models (Hyp and Gy) describe both conductive and sensorineural hearing impairment. Mouse models demonstrate high Auditory Brainstem Response (ABR) thresholds and signs of osteomalacia of auditory ossicles and ELH. In conclusion, there is an association between hearing loss in XLH and, most commonly, adult-onset sensorineural hearing loss. Pathogenesis of hearing loss in XLH is incompletely understood, but possible contributing factors include thickening of the temporal bones, osteomalacia of the auditory ossicles, and development of ELH. There is currently no evidence that treatment with conventional therapy or burosumab reduces the risk or severity of hearing impairment.