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Otolaryngology Research Increasingly Supports Genetic Screening to Evaluate Pediatric Hearing Loss

by Deborah Levenson •

Dr. Liu is looking ahead to the day when sequencing all of the protein-

coding genes with whole exome sequencing, and even the entire genome, may inform care for hearing loss. With National Institutes of Health grants, he has developed a 64-gene panel test for causes of deafness; he is also identifying and setting up a database of new genes and their function in human hearing loss and has made additional changes to the testing scenario described in his paper. GJB2 and GJB6 are still the first tests, along with mitochondrial DNA for patients with a maternal family history. If no cause is identified, patients get the panel test. If that is negative, they are eligible for either whole exome sequencing or whole genome sequencing.

Dr. Liu hopes his use of these technologies can spot new genetic causes and diagnose them in patients. Noting widespread predictions that the cost of sequencing a genome will soon drop to $1,000, he predicts that the technology will “change our way of testing and medical practice.”

Genomic Testing: Not for Everyone

Many hearing loss specialists familiar with exome and whole genome sequencing find its potential as a tool for diagnosing rare hereditary causes of hearing loss exciting, but some note disadvantages.

Genomic data has no practical use without complicated, costly bioinformatics analysis, which costs far more than sequencing and can yield extraneous information that can’t be interpreted, said Dr. Buchman. In addition, such sequencing brings with it several ethical issues, especially those concerning proper informed consent, added Dr. Lalwani.

Recent guidelines from the American College of Medical Genetics and Genomics direct laboratories to include in every report about genomic sequencing information about mutations in 57 genes that greatly increase the risk of developing 24 serious but treatable diseases—even if clinicians do not suspect a patient has one of those conditions. Included on the list are mutations known to increase the risk of breast cancer, ovarian cancer, Lynch syndrome and colorectal adenomas, which do not strike until adulthood. Lab reports about genomic test results for children should include mutations, says ACMG.

Not all parents will want this information, and otolaryngologists may not be prepared for it, either. The specified genetic mutations cause mainly hereditary cancer and cardiovascular disease that otolaryngologists do not diagnose or treat, said Dr. Smith. “How would otolaryngologists deal with and counsel their patients about this extra information?” he asked. “They would be expected to.”