Universal screening for newborn hearing loss and Early Hearing Detection and Intervention (EHDI) programs have become a standard of care in many states. With the recent identification of genes associated with hearing loss, genetic testing and counseling is becoming an integral component in these early intervention programs. Over 100 genes have been found to be associated with hearing loss; however, more than half of infants with non-syndromic sensorineural hearing loss will have mutations in only two genes, GJB2 (gap junction beta 2) and GJB6 (gap junction beta 6) making these mutations the most common cause of hereditary hearing impairment. These genes are located on chromosome 13 and produce the protein connexin 26, which is found in the cochlea. Connexin 26 creates gap junctions responsible for maintaining potassium levels in the cochlear endolymph. Gene mutations affect gap junction function and lead to sensorineural hearing loss. Patients with GJB2/GJB6 related hearing loss tend to have moderate to profound bilateral prelingual nonprogressive hearing impairment.

It is estimated that approximately 30 percent of infants with hearing loss will have one of more than 400 genetic syndromes associated with hearing impairment. Many of the physical findings associated with these syndromes may be hidden in early infancy. For example, Pendred syndrome (hearing loss, thyroid abnormalities), Jervell and Lange-Neilson syndrome (hearing impairment and cardiac arrhythmias), Usher syndrome (hearing loss, retinitis pigmentosa, and vestibular abnormalities), and Alport syndrome (hearing impairment and renal tubular dysfunction), may not have any observable abnormalities until later in childhood. Identification of these disorders requires blood testing, electrocardiograms, urinalysis, ophthalmologic evaluations, and computed tomography of the temporal bones.

Identification of GJB2/GJB6 mutations as part of the EHDI process may help with treatment decisions, and also potentially avoid unnecessary invasive adjunctive testing. Accordingly, the American College of Medical Genetics recommends genetic evaluation by a clinical geneticist for all children with hearing loss. This evaluation serves to determine whether the cause of hearing loss is genetic, environmental, syndromic, or non-syndromic. It also may identify recurrence chance, and allow for recommendations for additional testing and follow-up.

The complexity of genetic test results and impact on family members remains a volatile issue among several interested parties. While there is widespread agreement in the deaf community and in parents of deaf and hearing-impaired children that genetic testing in the newborn period would be beneficial, controversy remains in the area of genetic testing for hearing loss. For example, the eugenics movements in the early twentieth century led to recommendations advising against marriage between individuals with hearing loss. The concept of hearing loss being an 'undesirable' trait has also lead to some concerns in the deaf and hard-of-hearing community that genetic testing will lead to devaluation and/or elimination of individuals with hearing loss.

Currently, the role of genetic testing in the EHDI process is undefined. The importance of combining genetic testing with genetic counseling is becoming clear in providing families with adequate understanding and decision-making options in further treatment and evaluations for their infants and families. A new study identifies potential gaps in parental understanding of genetic information they obtain. The authors of "Impact of Genetic Testing and Counseling on Parental Understanding and Attitudes of Infants with Hearing Loss" are Nina L. Shapiro, MD, Ariadna Martinez, Milhan Telatar PhD, Michelle Fox, Barbara Crandall, MD, Wayne W. Grody MD PhD, Yvonne Sininger PhD, , Christina GS Palmer PhD, all from the University of California-Los Angeles, and Lisa A. Schimmenti MD, from the University of Minnesota. Their findings will be presented at The Twentieth Annual Meeting of the American Society of Pediatric Otolaryngology (ASPO) aspo.us being held May 27-30, 2005, at the J.W. Marriott Las Vegas Resort in Las Vegas, NV.

Methodology: At the UCLA Medical Center, 61 parents of 48 infants with apparent non-syndromic (or not related to a syndrome) hearing loss were enrolled in a prospective study including genetic testing (GJB2/GJB6 mutation analysis), results disclosure, genetic counseling, and parental questionnaire prior to and one month following genetic testing results. Questionnaires included understanding of inheritance concepts and perceived benefits and risks of genetic testing. The intervention of the study included infant buccal swab for DNA analysis, parental genetic counseling, and written questionnaires. The main outcomes measures were mutation analysis results, parental understanding of testing results and perceived benefits and risks of genetic testing prior to and following test result disclosures.

Results: Of the 48 infants, 14 were GJB2/GJB6 positive and 34 were GJB2/GJB6 negative. Of these, nine GJB2/GJB6 positive and 14 GJB2/GJB6 negative families participated in genetic counseling and questionnaires.

The researchers found correct responses were excellent both prior to and after results disclosure in all groups. However, there were several equivocal responses in the GJB2-negative group regarding understanding concepts of heterogeneity and inheritance. While GJB2-positive families also demonstrated some equivocal responses, the disparity was more notable in the GJB2-negative group. Specifically, questions regarding whether or not children can inherit hearing loss if neither parent has hearing loss, presence of hearing loss in babies with two abnormal connexin 26 genes, and recurrence chances of hearing loss if both parents are carriers of abnormal connexin 26 genes were misinterpreted more in the GJB2-negative group than in the GJB2-positive group. On the other hand, the GJB2-negative group had a better understanding that infants with two normal connexin 26 genes may still have hearing loss, and that babies with hearing loss need not have two abnormal connexin 26 genes, as was explained to them about their GJB2-negative infant with hearing loss. Both groups had an equal understanding that hearing loss may be inherited (100 percent correct in both groups).

Conclusions: The preliminary results of this study show that parents who were given non-diagnostic results (GJB2 negative group) had greater difficulty in understanding the meaning of test results, and demonstrated considerable variability in their understanding of recurrence chance. They were also less likely to feel that the test helped them understand cause of their child's hearing impairment. This underscores the complexity of providing negative test results and the need for development of genetic counseling strategies to enhance parental understanding of non-diagnostic test results.

Families without GJB2/GJB6 mutations need clinical genetic evaluations to assess possibility of syndromic diagnosis. Further investigations may include temporal bone computed tomography, evaluation for prenatal infections such as toxoplasmosis, herpesvirus, syphilis, and cytomegalovirus, renal ultrasound, urinalysis, electrocardiogram, thyroid studies, and ophthalmologic evaluation. However, prior to embarking on extensive diagnostic work-ups, the results thus far indicate that these families in particular need careful and well-presented genetic counseling to better understand the test results and future implications of these results.

American Society of Pediatric Otolaryngology (ASPO)
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