X-linked Alport syndrome: pathogenic variant features and further auditory genotype-phenotype correlations in males

ObjectiveTo analyze the clinical audiological characteristics of X-Linked Alport syndrome (XLAS) in males and their relationships with genotypes.MethodsThe clinical data of 87 male patients with AS were reviewed. Hearing levels were evaluated using pure tone audiometry (PTA) testing, acoustic immittance, and otoacoustic emissions (OAE) testing. The genotypes of COL4A5 and the pathogenic variants were analyzed. The relationships between auditory phenotypes and genotypes were analyzed.ResultsAmong the 87 patients, the number of patients with normal hearing and hearing loss were 32 and 55, respectively. In all cases, the hearing loss was characterized as bilateral symmetrical sensorineural deafness. Majority of the patients had mild-to-moderate hearing loss. Hearing loss usually started in the middle frequency range and gradually affected high frequencies, at school age and gradually increased with increasing age. However, it maintained a relatively steady level of 50-60dB HL during the teenage years. The audiometric curves included groove-type in 51 cases (92.73%). Patients were identified to have 60 different COL4A5 pathogenic variants. Of the 49 patients who were followed-up for more than 2years, 28 cases presented a decreasing trend in the hearing level of about 5dB per year. The degree of hearing loss was positively correlated with gene mutation type and renal function.ConclusionsHearing loss in males with XLAS is symmetrical sensorineural, and progressive with increasing age. There is a significant correlation between the degree of hearing loss and genotype, renal function, and age.