Auditory and otologic profile of Alström syndrome: Comprehensive single center data on 38 patients

Abstract

Alström syndrome is a rare autosomal recessive ciliopathy caused by mutations in the ALMS1 gene. Hallmark characteristics include childhood onset of severe retinal degeneration, sensorineural hearing loss, obesity, insulin-resistant diabetes, and cardiomyopathy. Here we comprehensively characterize the auditory and otologic manifestations in a prospective case series of 38 individuals, aged 1.7-37.9 years, with genetically confirmed Alström syndrome. Hearing loss was preceded by retinal dystrophy in all cases, and had an average age of detection of 7.45 years (range 1.5-15). Audiometric assessments showed mean pure tone averages (0.5, 1, 2, 4 kHz) of 48.6 and 47.5 dB HL in the right and left ears, respectively. Hearing was within normal limits for only 8/74 ears (11%). For the 66 ears with hearing loss, the degree was mild (12%), moderate (54%), or severe (8%). Type of hearing loss was predominantly sensorineural (77%), while three ears had mixed loss, no ears had conductive loss, and type of hearing loss was indeterminate for the remaining 12 ears. Serial audiograms available for 33 patients showed hearing loss progression of approximately 10-15 dB/decade. Our data show that hearing loss associated with Alström syndrome begins in childhood and is a predominantly symmetric, sensory hearing loss that may progress to a severe degree. Absent otoacoustic emissions, intact speech discrimination, and disproportionately normal auditory brainstem responses suggest an outer hair cell site of lesion. These findings indicate that individuals with Alström syndrome would benefit from sound amplification and if necessary, cochlear implantation.

Consensus clinical management guidelines for Alström syndrome

“…Absent oto-acoustic emissions with intact speech discrimination and normal auditory brain stem responses points to a cochlear origin [ 25 – 31 ]. The pathogenesis is thought to be due to the alteration of outer hair cells of the cochlea that occurs after birth [ 32 , 33 ]. In addition to the neurosensorial dysfunction, a conductive component can occur.…”

Clinical characteristics of individual organ system disease in non-motile ciliopathies

“…Hearing loss in AS is preceded by retinal dystrophy in all cases [95,102]. The majority of newborns with AS pass the newborn hearing screening [102].…”

“…Hearing loss in AS is preceded by retinal dystrophy in all cases [95,102]. The majority of newborns with AS pass the newborn hearing screening [102]. The rate of progression of hearing loss in AS is estimated at approximately 10-15 dB per decade [102].…”

“…The majority of newborns with AS pass the newborn hearing screening [102]. The rate of progression of hearing loss in AS is estimated at approximately 10-15 dB per decade [102]. Absent otoacoustic emissions, intact speech discrimination, and disproportionately normal auditory brainstem responses map the auditory defect in AS to the outer hair cells of the cochlea.…”

“…Absent otoacoustic emissions, intact speech discrimination, and disproportionately normal auditory brainstem responses map the auditory defect in AS to the outer hair cells of the cochlea. Therefore, AS patients are good candidates for traditional aural amplification or, in cases of severe to profound hearing loss, cochlear implantation [102].…”