Alström Syndrome: Progressive Deafness and Blindness

Welsh, Louis W.

doi:10.1177/000348940711600411

Cited by 21 publications

(15 citation statements)

References 16 publications

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“…Consistently, patients with multisystem ciliopathies such as Alström, Bardet-Biedl and Joubert syndromes often suffer from impairment of retinal, olfactory and auditory function. Progressive SNHL is a well-known feature of AS [Welsh et al, 2007]. However, age of onset and severity of hearing loss is variable.…”

Section: Discussionmentioning

confidence: 99%

“…While progressive decline in pure tone sensitivity has been documented in patients with AS [Bahmad Jr. et al, 2014; Welsh et al, 2007], the auditory profile has not been fully characterized. Distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs), which are critical assessments for discerning sensory versus neural hearing loss, have been reported for two siblings [Bahmad Jr. et al, 2014], but have not been reported for a cohort study.…”

Section: Introductionmentioning

confidence: 99%

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

Lindsey

Brewer

Stakhovskaya

et al. 2017

American J of Med Genetics Pt A

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lindsey

Brewer

Stakhovskaya

et al. 2017

American J of Med Genetics Pt A

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“…However, age of onset and severity is variable and can develop anytime from onset in infancy to adulthood [21,22]. Further, chronic and acute otitis media in childhood often exacerbates the sensorineural deficits with a component of conductive hearing loss [4].…”

Section: Alström Syndrome Clinical Overviewmentioning

confidence: 99%

Alstrom Syndrome: Genetics and Clinical Overview

Marshall

Maffei²,

Collin³

et al. 2011

230

298

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Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background.Alström syndrome is caused by mutations in ALMS1, a large gene comprised of 23 exons and coding for a protein of 4,169 amino acids. In general, ALMS1 gene defects include insertions, deletions, and nonsense mutations leading to protein truncations and found primarily in exons 8, 10 and 16. Multiple alternate splice forms exist. ALMS1 protein is found in centrosomes, basal bodies, and cytosol of all tissues affected by the disease. The identification of ALMS1 as a ciliary protein explains the range of observed phenotypes and their similarity to those of other ciliopathies such as Bardet-Biedl syndrome.Studies involving murine and cellular models of Alström syndrome have provided insight into the pathogenic mechanisms underlying obesity and type 2 diabetes, and other clinical problems. Ultimately, research into the pathogenesis of Alström syndrome should lead to better management and treatments for individuals, and have potentially important ramifications for other rare ciliopathies, as well as more common causes of obesity and diabetes, and other conditions common in the general population.

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“…Greater than 85% of patients present with bilateral sensorineural hearing loss, usually beginning in the first decade of life. The hearing loss is often compounded by chronic otitis media and glue ear [Alström et al, 1959, Marshall et al 2005, Marshall et al 2007,Welsh 2007, Marshall et al 2011]. Other clinical features include truncal obesity, type 2 diabetes mellitus in 95% of children over the age of 15 years, hypertriglyceridemia, hypercholesterolemia, dilated or restrictive cardiomyopathy, hypogonadism, glomerulosclerosis leading to progressive renal failure, steatosis, steatohepatitis, or cirrhosis of the liver [Marshall et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

Histopathology of the Human Inner Ear in Alström's Syndrome

2015

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Alström's syndrome is an autosomal recessive syndromic genetic disorder caused by mutations in the ALMS1 gene. Sensorineural hearing loss occurs in greater than 85% of patients. Histopathology of the inner ear abnormalities in the human has not previously been fully described. Histopathology of the inner ear in Alström's syndrome is presented in 2 genetically confirmed cases. The predominant histopathologic correlates of the sensorineural loss were degeneration of the organ of Corti, both inner and outer hair cells, degeneration of spiral ganglion cells, and atrophy of the stria vascularis and spiral ligament.

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Alström Syndrome: Progressive Deafness and Blindness

Cited by 21 publications

References 16 publications

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

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

Alstrom Syndrome: Genetics and Clinical Overview

Histopathology of the Human Inner Ear in Alström's Syndrome

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