Sensorineural hearing loss (SNHL) occurs in 4/1000 newborns. Until recently the work-up used a """"""""shotgun"""""""" approach; many tests were ordered but the etiology remained unknown in 50% of cases. However, the recent use of genetic testing and high-resolution imaging has increased the yield of the SNHL evaluation. Mutations in the connexin 26 gene (Cx26) are responsible for approximately 50% of all recessive nonsyndromic SNHL allowing Cx26 gene testing to greatly expand the ability to provide an etiology for SNHL. This information can provide diagnostic as well as prognostic information to the patients, their families, and their physicians. The current proposal seeks to address several areas that have not been addressed by our studies or those of others. First, the audiologic phenotype of infants and children with SNHL and Cx26 mutations, both at the time of presentation and longitudinally, needs further definition. Second, it is not clear whether the audiologic phenotype varies with specific mutations or combination of mutations. Third, it is not clear whether CT scans of the temporal bones are ever routinely indicated in a patient with biallelic Cx26 mutations. Finally, in families of children with SNHL, it is not clear how well patients and families are being counseled to understand the benefits, drawbacks, and limitations of genetic testing or the results and implications of their genetic tests. It is also unclear why parents choose or decline genetic testing, and whether proper consent is obtained for such testing. We propose a clinical study to evaluate infants and children with Cx26-related nonsyndromic SNHL. To accomplish these aims we will use 2 large patient populations from Children's Hospital Boston (CHB) including 1.Newborns referred after failing a newborn hearing screen; 2.Non-newborns with newly identified SNHL. There are four areas of concentration: 1.) Identification of Cx26 positive infants and children using genetic testing as part of the initial evaluation for newly-identified SNHL. 2.) The phenotype of the Cx26 related hearing loss will be studied, both at the time of diagnosis and prospectively over time. The rate and percentage of progression of Cx26 related hearing loss will also be evaluated. 3.) The diagnostic evaluation of the hearing loss will include temporal bone imaging studies, as the presence of anatomic temporal bone abnormalities is frequently associated with progression of the hearing loss and thus would affect the prognosis if present. Although temporal bone abnormalities have not been sought in large numbers of Cx26 positive patients, they are thought to be uncommon, at least for the two most frequently identified mutations, 35deIG and 67delT. However, recent studies suggest that temporal bone abnormalities may be present in some patients with Cx26 mutations. If this were so, the prognosis of the hearing loss would be affected. 4.) For families of children with SNHL, we will utilize a questionnaire to determine why parents choose to have/not have genetic testing and to ascertain parents understanding of genetic testing. This information will be used to evaluate the effectiveness of genetic counseling associated with gene testing for deafness.
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