Auditory function and hearing loss in children and adults with Williams syndrome: Cochlear impairment in individuals with otherwise normal hearing

Abstract

Hearing loss is common in school-age individuals with Williams syndrome (WS) and extensive in adults. Prior studies with relatively small sample sizes suggest that hearing loss in WS has an early onset and may be progressive, yet the auditory phenotype and the scope of the hearing loss have not been adequately characterized. We used standard audiometric tools: Otoscopy, tympanometry, air-conduction (bone conduction when available) behavioral testing, and distortion product otoacoustic emissions (DPOAEs) to measure hearing sensitivity and outer hair cell function. We tested 81 individuals with WS aged 5.33 to 59.50 years. 63% of the school-age and 92% of the adult participants had mild to moderately-severe hearing loss. The hearing loss in at least 50% was sensorineural. DPOAE testing corroborated behavioral results. Strikingly, 12 of 14 participants with hearing within normal limits bilaterally had 4000-Hz DPOAE input/output (DPOAE IO) functions indicative of outer hair cell damage and impaired cochlear compression. Our results indicate that hearing loss is very common in WS. Furthermore, individuals with WS who have “normal” hearing as defined by behavioral thresholds may actually have sub-clinical impairments or undetected cochlear pathology. Our findings suggest outer hair cell dysfunction in otherwise normal hearing individuals. The DPOAE IO in this same group revealed growth functions typically seen in groups with noise-induced damage. Given this pattern of findings, individuals with WS may be at increased risk of noise-induced hearing loss. Recommendations regarding audiological testing for individuals with WS and accommodations for these individuals in both academic and nonacademic settings are provided.

The behavioral phenotype of Williams syndrome: A recognizable pattern of neurodevelopment

“…Adults typically have a stiff awkward gait characterized by reduced speed and stride length [Hocking et al, 2009]. Sensorineural hearing loss is common in both children and adults, and many are noted to be hypersensitive to sound [Gothelf et al, 2006;Marler et al, 2010]. Advances in neuroimaging techniques show subtle structural differences in WS.…”

Cochlear active mechanisms in young normal-hearing subjects affected by Williams syndrome: Time–frequency analysis of otoacoustic emissions

“…Cherniske et al, 2004;Johnson et al, 2001;Marler et al, 2010). Hearing loss in WS subjects has, typically, early onset and is hypothesized to be progressive (Gothelf et al, 2006;Marler et al, 2005Marler et al, , 2010.…”

The role of GTF2IRD1 in the auditory pathology of Williams–Beuren Syndrome

“…[15][16][17][18] However, there is no evidence in our mice of a mechanism within the auditory signal processing pathway that might explain the auditory allodynia in WBS patients. 32 It is possible that this phenomenon results from Figure 5 Distortion products otoacoustic emission (DPOAE) thresholds.…”

“…[13][14][15] SNHL in WBS has been shown to be progressive and the prevalence may develop to~80% of subjects over time. 16 Although many younger WBS patients seem to have hearing in the normal range, it is generally agreed that analysis of otoacoustic emissions from the cochlea of these patients indicates high rates of abnormalities, [15][16][17][18] suggesting a degree of 'cochlear fragility', 15 associated with altered sound transduction. Measurement of the distortion product of otoacoustic emissions (DPOAEs) is a non-invasive, highly sensitive, objective measure of the cochlear amplifier mechanism mediated by the outer hair cells.…”

“…16 The cause of the auditory pathology in WBS is currently unknown and has led some to speculate on a possible contribution from the observed effects of premature ageing and/or a high predisposition for noise-induced cochlear damage that could be connected to the so-called hyperacusis. 17 Involvement of the haploinsufficiency of elastin due to hemizygous loss of the ELN gene is a popular hypothesis 15,17,18 because of its profound impact on other organ systems and expression of the gene in several key hearing structures. Loss of the LIMK1 gene has also been implicated as it encodes a kinase that regulates actin reorganisation and has a role in the control of outer hair cell motility.…”