Clinical Analysis Of Disorders Of Hearing And Balance

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1. In collaboration with Drs. Morell and Friedman of the SHG, our audiology unit has used a battery of tests of central auditory and speech processing in a large cohort of monozygotic and dizygotic twins in order to test the hypothesis that one or more measurable parameters of these phenomena are heritable, They have determined that performance on at least one of the tests shows a very high heritability. This particular trait may be amenable to molecular genetic approaches to identify the genes underlying the observed variation. 2. We are using pure-tone audiometry in a large cohort of monozygotic and dizygotic twins, 50 years of age or older, to estimate the proportion of age-related hearing loss (presbycusis) that is due to genetic factors. We have completed the first pilot phase of this study and are currently analyzing our zygosity test and audiometric test results. This is an important study since the results will determine whether it will be fruitful to search for genetic determinants of presbycusis or whether our public health and education efforts should be more focused on prevention of exposure to ototoxic agents such as loud noise. 2. In collaboration with Dr. Drayna of the Laboratory of Molecular Genetics, our audiology unit used a battery of audiologic tests to detect auditory physiologic abnormalities associated with tune deafness. They identified at least one test in which performance is strongly correlated with tune deafness. The study is completed and a manuscript is being prepared for submission for publication. 3. In collaboration with Dr. Al Braun and others, the audiology unit is involved in the design, implementation, and data analysis of safety studies on the auditory system (and hearing) after exposure to either multiple MRI scans, or MRI scans performed in new scanners. 4. The Hearing Section conducts the auditory phenotypic assessment of individuals with hearing loss and enlarged vestibular aqueducts (EVA), as well as their siblings and parents. About 90 probands and their families have now been ascertained, and the audiologic data reveals a correlation of the auditory phenotype with the underlying SLC26A4 (PDS) genotype. The audiology unit is currently evaluating details of the auditory phenotype to search for features that predict genotype, clinical prognosis, or clinical diagnosis. 5. In collaboration with investigators from other NIH institutes, we continue to evaluate hearing and balance manifestations in Turner syndrome (Dr. Bondy, NICHD), Fanconi anemia and other inherited bone marrow failure syndromes (Dr. Alter), neonatal onset multi-system inflammatory disorder (Dr. Goldbach-Mansky, NIAMS), familial cold urticaria/MuckleWells syndrome (Dr. Goldbach-Mansky, NIAMS), Fabry disease (Dr. Schiffman, NINDS), Pallister-Hall syndrome (Dr. Biesecker, NHGRI), Smith-Magenis syndrome (Ms. Smith, NHGRI), Usher syndrome (Dr. Tsilou, NEI), xeroderma pigmentosum (Dr. Kraemer, NCI), progeria (Dr. Gordon, NHGRI), McCune-Albright syndrome and Polyostotic Fibrous Dysplasia (Dr. Collins, NIDCR), and anthrax (Dr. Wright, NIAID). 6. In collaboration with Dr. Goldbach-Mansky, the audiology unit characterized hearing and balance status in NOMID patients undergoing a clinical therapeutic trial of interleukin-1 beta inhibition. They found there was neither a positive nor negative effect on hearing during or after treatment. 7. The Audiology Unit completed an analysis of the clinical phenotype of eight affected members of a large family segregating autosomal dominant, nonsyndromic, postlingual-onset, progressive sensorineural hearing loss caused by a mutation of the EYA4 gene at the DFNA10 locus. 8. In collaboration with Dr. Leopold (NIMH), the audiology unit is involved in the design, implementation, an analysis of safety studies on the auditory system in macaque monkeys exposed to functional MRI noise. 9. We ascertained a large North American family segregating progressive, nonsyndromic sensorineural hearing loss in a matrilineal/maternal/mitochondrial pattern of inheritance. The hearing loss phenotype is remarkable for its high degree of penetrance, early onset and rapid progression, and numerous anecdotal reports of sudden drops of hearing associated with head trauma.