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

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 5.33-59.50 years. Sixty-three percent 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 4,000-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.

Sensory processing of backward-masking signals in children with language-learning impairment as assessed with the auditory brainstem response.

The purpose of this study was to examine the possible contribution of sensory mechanisms to an auditory processing deficit shown by some children with language-learning impairment (LLI). Auditory brainstem responses (ABRs) were measured from 2 groups of school-aged (8-10 years) children. One group consisted of 10 children with LLI, and the other group (control) consisted of 10 children with normally developing language. The ABR was elicited with a brief tone burst presented either alone (no-masking condition) or immediately followed by a longer duration noise burst (backward-masking condition). The primary dependent variable was the latency of wave V of the ABR. The mean latencies were not significantly different for the 2 groups in the no-masking condition. However, in the backward-masking condition, the mean latency for the LLI group was significantly increased relative to the mean latency for the control group. Thus, the presence of successive sounds delay the neural response in children with LLI. The explanation for this delay at the level of the brainstem is not known, but it may be due to disruption of synchrony, activation of alternate (less direct) pathways, increased inhibition, or some combination of these (or other) factors.

Qualitative characterization of elastic fiber distribution in the mouse vocal fold: further development of an animal model.

The purpose of this study was to identify the presence and characteristics of the distribution patterns of elastic fibers in a 15-week-old C57BL/6J mouse vocal fold, to confirm the presence and distribution of collagen fibers, and to describe potential gender differences in staining patterns, with the aim of further developing the mouse model for use in translational research of vocal fold physiological mechanisms. The vocal folds from 12 mice, divided equally into gender categories, were stained for elastic fibers and collagen fibers using conventional staining methods. Qualitative (subjective) visual analyses were performed by identifying the staining density of elastic and collagen fibers in the superficial half and deep half of the vocal fold lamina propria. Analyses revealed the presence of elastic fibers in both male and female vocal folds, although patterns of staining density were heavy in the deep half of the lamina propria, a location that is deeper than the greatest concentrations of elastic fibers in human vocal folds. Collagen fibers were also present in locations similar to those within human vocal folds, consistent with previously published data. The results of this study support the use of the mouse model in translational and basic science research, and this model may be especially useful for research aimed at furthering our knowledge of genetic influences on vocal fold structural development and function.

An investigation of voice quality in individuals with inherited elastin gene abnormalities.

The human elastin gene (ELN) is responsible for the generation of elastic fibres in the extracellular matrix of connective tissue throughout the body, including the vocal folds. Individuals with Supravalvular aortic stenosis (SVAS) and Williams syndrome (WS) lack one normal ELN allele due to heterozygous ELN abnormalities, resulting in a haploinsufficiency. We measured perceptual and acoustic characteristics of voice quality in individuals with SVAS and WS to investigate the consequences to vocal function secondary to ELN haploinsufficiency. Results indicated that the voice quality of individuals with SVAS/WS was rated as significantly more abnormal, rough, and hoarse compared to normal controls, and that adults with SVAS/WS were rated as significantly lower in pitch. Acoustic measures indicated that individuals with SVAS/WS produced greater instability of fundamental frequency during phonation (as reflected via increased pitch sigma and increased jitter). These findings support the possibility that heterozygous ELN abnormalities negatively influence vocal fold biomechanics and the resulting sound produced by the vibrating glottis.

Sensorineural hearing loss in children and adults with Williams syndrome.

Williams syndrome (WS) is a genetic neurodevelopmental disorder, most often accompanied by mild-to-moderate mental retardation. Individuals with WS show unique communication strengths and impairments that are challenging to treat in community, educational, and vocational settings. Many issues regarding characteristics of auditory sensitivity in WS remain to be resolved. Our purpose was to obtain behavioral (screening and pure-tone audiometry) and objective (distortion product otoacoustic emission-DPOAE) measures of auditory system function from a group of 27 individuals with WS, 6-48 years of age. These measures were gathered both at an international professional conference (n = 19) and in a clinic setting (n = 8). In the behavioral screening conditions, 16/19 (84%) of the individuals failed the hearing screening; and in the behavioral diagnostic hearing condition, 6/8 (75%) demonstrated sensorineural hearing loss (SNHL) and 1/8 demonstrated a hearing loss of undetermined type. In the objective DPOAE testing, 19/25 (76%) had DPOAE absolute amplitudes below the 5th percentile for ears with normal hearing [Gorga et al. (1997); Ear Hear 18(6):440-455]. We report SNHL in 14/18 (78%) of school-age children with WS. Post hoc analyses revealed a significant effect for age, suggesting a pattern of progressive hearing loss. An effect size analysis indicated a clinically meaningful difference in the hearing sensitivity between school-aged children and adults in the high frequencies (4,000 and 8,000 Hz). Similar hearing loss phenotype was observed in patients with familial nonsyndromic supravalvular aortic stenosis (SVAS), suggesting that molecular defects in the elastin gene in the pathogenesis of SNHL in WS. This study highlights the importance of early and regular hearing testing for WS patients and suggests that elastin may have a previously unappreciated function in maintaining hearing sensitivity.

Auditory memory for backward masking signals in children with language impairment.

This study was designed to investigate early auditory memory and its possible contribution to an auditory processing deficit shown by some children with language impairment. Ten children with language impairment and 10 age-matched controls participated in a series of simultaneous and backward masking tasks. The same backward masking stimulus was then used to elicit a mismatch negativity response. In the behavioral conditions, children in the language impairment group had significantly higher (poorer) signal thresholds than their nonimpaired controls in backward masking, but their thresholds in simultaneous masking were not significantly different. In the mismatch-negativity conditions, latency was prolonged and the amplitude was diminished in the children with language impairment. Taken together, these psychoacoustic and electrophysiological data suggest that in a group of children with language impairment, underlying the nonsensory language disorder, there is a neurophysiological impairment in auditory memory for complex, nonlinguistic sounds.