Is Hearing Loss an Extracolonic Manifestation of FAP?

Abstract

Purpose: FAP is due to a mutation in the APC gene. It is a recent discovery that APC protein dysfunction results in abnormal cytoskeletal organization of the cochlea of Min mice heterozygous for APC when compared to wild type litter mates (Mogensen M, J Cell Bio 2002). The hearing of FAP patients has never been studied. We performed audiograms in FAP patients to determine their hearing thresholds and report the characteristics of hearing impairment in FAP. Methods: Patients who denied hearing loss and were being screened for eligibility in an international, multicenter, polyp chemoprevention study (Cleveland, London, Houston) underwent air-conduction, pure-tone audiogram after a normal otoscopic exam. We compared the audiometric results of the patients to gender and age-adjusted hearing threshold normative values. The normative values represent hearing in which at least 95% of the population have equal or better hearing (Morrell C, et al. J Acoust Soc Am 1996). Patients who didn't meet audiometric norms were considered to have hearing loss. Characteristics of patients who failed audiometry including age, and gender and the associated audiometric abnormalities (laterality and frequency (ies)) of hearing loss were analyzed. Results: 140 patients (65 women/75 men); mean age of 37.1 yrs (range 18–64) were tested. 41 patients (29.3%) failed the audiogram. Hearing loss was not associated with gender but was more common in younger patients. It was detected in 53.8% of patients between ages 18–25, 34.8% ages 26–35, 17.6% ages 36–45, 14.3% age 46–55 and 22% ages 56–65, p < 0.001. Hearing loss was more often bilateral vs unilateral (56.1 vs 43.9, p= 0.43). Hearing loss of multiple frequencies was more common than single frequency (65.9% vs 34.2%, p= 0.042). Higher frequency hearing loss was more common than lower frequency (p= 0.05) hearing loss. A greater percentage of patients failed their audiogram at the Cleveland site (50%) versus Texas 27.4% or London 22.5% (p= 0.038). Conclusions: These data are the first report of hearing loss in humans with FAP and support the abnormal cell biology found in the cochlea of Min mice. Subclinical hearing loss occurs commonly in FAP but the clinical implications are unknown. Audiometric screening of FAP patients should be considered and genotype phenotype correlations should be explored.