TY - JOUR
T1 - Auditory and otologic profile of Alström syndrome
T2 - Comprehensive single center data on 38 patients
AU - Lindsey, Spencer
AU - Brewer, Carmen
AU - Stakhovskaya, Olga
AU - Kim, Hung Jeffrey
AU - Zalewski, Chris
AU - Bryant, Joy
AU - King, Kelly A.
AU - Naggert, Jürgen K.
AU - Gahl, William A.
AU - Marshall, Jan D.
AU - Gunay-Aygun, Meral
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/8
Y1 - 2017/8
N2 - Alström syndrome (AS) 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 AS. 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 AS 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 AS would benefit from sound amplification and if necessary, cochlear implantation.
AB - Alström syndrome (AS) 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 AS. 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 AS 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 AS would benefit from sound amplification and if necessary, cochlear implantation.
KW - ALMS1
KW - Alström
KW - ciliopathy
KW - sensory hearing loss
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U2 - 10.1002/ajmg.a.38316
DO - 10.1002/ajmg.a.38316
M3 - Article
C2 - 28573831
AN - SCOPUS:85020072994
SN - 1552-4825
VL - 173
SP - 2210
EP - 2218
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 8
ER -