LAS VEGAS—Experts on sensorineural hearing loss (SNHL) gathered for a panel presentation entitled “Fluctuating and Progressive Sensorineural Hearing Loss in Children,” which convened during the Annual Meeting of the Triological Society, held here May 15-16 as a part of the Combined Otolaryngology Spring Meetings.
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August 2014Panel speakers gave reason for hope that new insights into the genetics of the disorder might help guide future treatment and that the field of otolaryngology is getting a better grasp on SNHL caused by cytomegalovirus (CMV).
Panel moderator Marci Lesperance, MD, professor of otolaryngology-head and neck surgery at the University of Michigan Health System in Ann Arbor, said the information presented was timely and on the cutting edge. “There’s some exciting research going on to help us really understand the causes of progressive hearing loss in children,” she said. “And by understanding the cause, we have the potential for having good interventions to offer in the future.”
“This is really a very frustrating clinical problem when you sometimes don’t have very much to offer the parents,” she added.
Genetic Mutations
Andrew J. Griffith, MD, PhD, chief of the molecular biology and genetics section of the otolaryngology branch of the National Institute on Deafness and Other Communication Disorders in Bethesda, Md., part of the National Institutes of Health, discussed how his laboratory has developed a mouse model with SLC26A4 gene mutations that mimic the human phenotype of hearing loss fluctuation. The mutations can cause hearing loss related to enlarged vestibular aqueducts.
SLC26A4 knockout mice are totally deaf and are not a good model for studying the typical human phenotype. But Dr. Griffith’s lab has developed a model in which the expression of SLC26A4 is controlled by putting the antibiotic doxycycline in the mice’s drinking water during the formation of the embryo (Neurobiol Dis. 2014;66:53-65).
Hearing tests show that the hearing thresholds of those mice fluctuate before getting progressively worse, similar to people with enlarged vestibular aqueducts. “We think this is a useful tool now to explore the cellular and molecular basis of hearing fluctuation,” he said.
Dr. Griffith and his colleagues have a few thoughts on what is happening in this situation. “We expect the blood-labyrinth barrier, which is the ear’s equivalent of the blood-brain barrier, is involved with this process and that could explain the drops in hearing we see with trauma,” he said. Another suspicion is that activation of the innate immune system plays a role, he said, as well as oxidative stress.
The model can be used to explore these questions and to test possible therapies, including immunomodulatory drugs and antioxidants, Dr. Griffith said.
Cytomegalovirus
Daniel Choo, MD, the director of pediatric otolaryngology-head and neck surgery at Cincinnati Children’s Hospital Medical Center, discussed the tricky nature of pediatric hearing loss caused by CMV infection.
There is only a two- or three-week window after birth when a child with hearing loss can have a test considered to be definitive for CMV hearing loss. After that, most become carriers or become infected, and the hearing loss can no longer be considered definitively CMV-related.
Studies out of the University of Alabama at Birmingham (UAB) have shown that treatment with parenteral ganciclovir can rescue hearing in some children, or at least stabilize hearing during their first year of life, Dr. Choo said.
When hearing issues arise later, the question is whether to retreat as a reactivation of CMV or explore other possibilities. “It ends up being a risk-benefit calculation,” Dr. Choo said, involving potential adverse events of antiviral treatment, the severity of the impairment, and the age of the patient. UAB researchers have found that two-thirds of patients either had to have their dose reduced or had to withdraw because of toxic events, most commonly bone marrow suppression.
At the University of Cincinnati, researchers are looking for potential guidance in immunoglobulin G (IgG) assays. “If you can’t test to tell if a child has active CMV infection versus just latent colonization, is there some way we can assay for that?” he said. They’ve found that at about two months after infection, your body generates a low-affinity IgG, and after about four months, you generate high-avidity IgGs. “We might be able to exploit that to determine if these kids are actually acutely infected and can be good targets for antiviral treatment,” Dr. Choo said.
New antivirals with less toxicity and better efficacy are being developed, he added. Additionally, University of Cincinnati researchers are exploring intratympanic delivery of medication, an option that would avoid exposing the entire body to toxicities. They’re also developing nanotechnology for delivery of drugs to the inner ear, he said (Antivir Ther. 2014;19:97-105).
Diagnostic Overload
Blake Papsin, MD, MSc, FRCSC, otolaryngologist-in-chief and professor of otolaryngology-head and neck surgery at the University of Toronto, said the algorithm for SNHL at his center does not call for automatic imaging and genetic testing.
If the child is old enough to be imaged without sedation and the parents are interested, then imaging and genetic testing are done. “But we don’t do it in everybody,” he said. If the problem is severe to profound, then the imaging and testing is done. If it’s not, then the child is followed at six-month intervals. If the hearing loss is found to be progressive, the imaging and testing is done.
“It’s phenotype-based,” Dr. Papsin said. “And it’s based upon the progression. That’s the start point for doing the testing. Up till then, I do nothing.”
But this approach is used within a system in which all children are captured, everyone who chooses to be is fully vaccinated, and there is a “reasonable medical legal environment” in which physicians are less afraid of being sued. “It’s the progressive hearing loss that’s the reason to proceed with the diagnostic algorithm,” he said. “There is no diagnostic algorithm without the progressivity. And it’s probably the only finding that justifies the expense of diagnostic testing.”
Dr. Choo said genetics testing and imaging can help guide discussions with parents. It may be that, “based upon the genotype, we really predict your kid’s going to be in the severe to profound range …. I’ll start planting the seeds about a cochlear implant for that kid fairly early.”
Dr. Griffith said that, in the case of the SLC26A4 gene, multiple mutations mean a worse outlook and a higher likelihood that siblings will be affected. “That has implications for the family,” he said, “because they try to predict what to expect.”
Thomas Collins is a freelance medical writer based in Florida.
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