Sensorineural hearing loss in children and adults with Williams syndrome

Marler, Jeffrey A.; Elfenbein, Jill L.; Ryals, Brenda M.; Urban, Zsolt; Netzloff, Michael L.

doi:10.1002/ajmg.a.30970

Cited by 60 publications

(71 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In older patients, mild to moderate high-frequency sensorineural hearing loss is described [Marler et al, 2005;Gothelf et al, 2006]. In our cohort 61% presented with hypoacusia with onset after 18 years of life, again demonstrating the importance of regular evaluations at this age.…”

Section: Discussionsupporting

confidence: 56%

Clinical follow‐up of young adults affected by Williams syndrome: Experience of 45 Italian patients

Bedeschi

Bianchi

Colli

et al. 2011

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Williams-Beuren syndrome (WBS) is a multisystem disorder that requires ongoing management by a primary care physician familiar with the natural history and specific medical problems associated with the condition. While the natural history of the disease during infancy is well known, data about the adult WBS population have been published only in the last few years, and show a wide range of medical, neurological, and psychiatric problems. We investigated 45 young adult WBS patients (mean age 23 years, range 17-39 years) using a well-coordinated team which included a cardiologist, a nephrologist, an ophthalmologist, an endocrinologist, a gastroenterologist, orthodontist, and orthopedist. Here we describe the clinical features and medical complications in this cohort of patients. Most patients demonstrated a high frequency of multiple organ systems complications, in particular, abnormal body habitus; cardiovascular disease, and hypertension; sensorineural hearing loss; gastrointestinal symptoms including diverticular disease and abnormal glucose tolerance. We offer some suggestions for clinical monitoring which we propose will be useful in the overall care of adults with WBS.

show abstract

Section: Discussionsupporting

confidence: 56%

Clinical follow‐up of young adults affected by Williams syndrome: Experience of 45 Italian patients

Bedeschi

Bianchi

Colli

et al. 2011

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Neurological problems include coordination diYculties (for example, trouble walking down a staircase), hyperreXexia, cerebellar dysfunction such as ataxia and dysmetria (Chapman et al 1996;Cherniske et al 2004), strabismus (esotropia) (Kapp et al 1995;Winter et al 1996), nystagmus, hypersensitivity to sound, and sensorineural hearing loss (Marler et al 2005). The hypotonia noted in young children typically improves in childhood (Chapman et al 1996).…”

Section: Neurological Problemsmentioning

confidence: 99%

Copy number variants at Williams–Beuren syndrome 7q11.23 region

et al. 2010

View full text Add to dashboard Cite

Copy number variants (CNVs) of the Williams-Beuren syndrome (WBS) 7q11.23 region are responsible for neurodevelopmental disorders with multi-system involvement and variable expressivity. Typical features of WBS microdeletion comprise a recognizable pattern of facial dysmorphisms, supravalvular aortic stenosis, connective tissue abnormalities, hypercalcemia, and a distinctive neurobehavioral phenotype. Conversely, the phenotype of patients carrying the 7q11.23 reciprocal duplications includes less distinctive facial dysmorphisms and prominent speech delay. The common deletion/duplication ranges in size from 1.5 to 1.8 Mb and encompasses approximately 28 genes. This region is flanked by low copy repeats (LCRs) with greater than ~97% identity, which can mediate non-allelic homologous recombination resulting from misalignment of LCRs during meiosis. A clear genotype-phenotype correlation has been established in WBS only for the elastin gene, which is responsible for the vascular and connective tissue abnormalities. The molecular substrates underlying the other clinical features of 7q11.23 CNVs, including the neurocognitive phenotypes, are still debated. Recent studies suggest that besides the role of the genes in the deleted/duplicated interval, multiple factors such as regulatory sequences, epigenetic mechanisms, parental origin of the CNV, and nucleotide variations in the non-deleted/duplicated allele may be important in determining the variable expressivity of 7q11.23 CNV phenotypes. Here, we review the clinical and molecular findings and the recent insights on genomic disorders associated with CNVs involving the 7q11.23 region.

show abstract

“…12 Several studies have shown that WBS patients of all ages show increased rates of mild to moderate high-frequency sensorineural hearing loss (SNHL). [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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

Williams-Beuren Syndrome (WBS) is a rare genetic condition caused by a hemizygous deletion involving up to 28 genes within chromosome 7q11.23. Among the spectrum of physical and neurological defects in WBS, it is common to find a distinctive response to sound stimuli that includes extreme adverse reactions to loud, or sudden sounds and a fascination with certain sounds that may manifest as strengths in musical ability. However, hearing tests indicate that sensorineural hearing loss (SNHL) is frequently found in WBS patients. The functional and genetic basis of this unusual auditory phenotype is currently unknown. Here, we investigated the potential involvement of GTF2IRD1, a transcription factor encoded by a gene located within the WBS deletion that has been implicated as a contributor to the WBS assorted neurocognitive profile and craniofacial abnormalities. Using Gtf2ird1 knockout mice, we have analysed the expression of the gene in the inner ear and examined hearing capacity by evaluating the auditory brainstem response (ABR) and the distortion product of otoacoustic emissions (DPOAE). Our results show that Gtf2ird1 is expressed in a number of cell types within the cochlea, and Gtf2ird1 null mice showed higher auditory thresholds (hypoacusis) in both ABR and DPOAE hearing assessments. These data indicate that the principal hearing deficit in the mice can be traced to impairments in the amplification process mediated by the outer hair cells and suggests that similar mechanisms may underpin the SNHL experienced by WBS patients.

show abstract

Sensorineural hearing loss in children and adults with Williams syndrome

Cited by 60 publications

References 42 publications

Clinical follow‐up of young adults affected by Williams syndrome: Experience of 45 Italian patients

Clinical follow‐up of young adults affected by Williams syndrome: Experience of 45 Italian patients

Copy number variants at Williams–Beuren syndrome 7q11.23 region

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

Contact Info

Product

Resources

About