Penn Otorhinolaryngology – Head and Neck Surgery is the first to have a dedicated Center focused on the genetics of adult-onset hearing loss. The program is a collaboration between the Departments of Genetics and Otorhinolaryngology and the Penn Medicine BioBank (PMBB). Participants active in the patient experience include Otology, Audiology, and Clinical Genetic Counselors and there are ongoing active collaborations with basic and translational researchers and with the PMBB and Department of Genetics. The Center’s mission is to identify the genetic underpinnings of adult onset hearing loss and develop novel therapeutic options to stop its progression or prevent it all together.
Each year, tens of thousands of adult patients obtain hearing aids and thousands more move on to cochlear implantation. For most of these individuals, a cause for hearing loss is never determined, and providers have no alternative therapies to offer. Those with severe or rapidly progressive hearing loss often undergo extensive and expensive investigations that too often return no answers and treatment trials that fail to halt or reverse hearing loss. Additionally, patients may be treated empirically with steroids or other immune suppressing medications, exposing them to potentially serious side effects.
Adult-onset hearing loss, a form of progressive deafness that affects one third of adults over the age of 60, has been linked to concerns common to hearing loss at any age—including social isolation and depression. Hearing loss has also been linked to decreased economic and educational success as well as cognitive decline.
The Enigma of Adult-Onset Hearing Loss
Despite substantial advances in our understanding of the genome and its implications for prognosis in hearing loss in children, the genetics of adult-onset hearing loss is largely a mystery. In early-onset hearing loss, we now know that about half of all cases in developed countries have a genetic etiology. Mutations in most of these genes result in non-syndromic sensorineural hearing loss (SNHL), a condition for which abnormal inner ear function is the only diagnostic feature.
“So far, we’ve found little among the 150 genes known to have a role in hearing and deafness to explain adult-one hearing loss,” says Michael Ruckenstein, MD, MSc, FACS
The specific genetic origins of most adult-onset hearing loss remain clinically undefined, however.
“So far, we’ve found little among the 150 genes known to have a role in hearing and deafness to explain adult-one hearing loss,” says Michael Ruckenstein, MD, MSc, FACS, who will lead the new Center for Adult-Onset Hearing Loss at the Perelman Center for Advanced Medicine. Dr Ruckenstein notes that while 80% of persons with hearing loss are diagnosed after the second decade of life, few adults undergo genetic testing even when a genetic source is suspected from family history.
“A general view among patients, unfortunately, is that there’s little point in genetic testing given the paucity of information available,” Dr. Ruckenstein says. “It’s a perception he hopes to change in the near future.”
Soundings: A New Approach to Hearing Loss Diagnosis and Therapy
Beyond the current standard of care for adults suffering from progressive hearing loss (serial audiograms, hearing aids, cochlear implants), patients at the Center for Adult-Onset Hearing Loss will have the voluntary option of analysis for genetic mutations known to be associated with hearing loss, as well as whole genome sequencing to help find mutations yet to be identified.
“This is really a paradigm shift in the way we evaluate patients with hearing loss,” Dr. Ruckenstein explains. “It means that for the first time we’ll be able to offer a diagnostic approach based on knowledge of what’s happening in the inner ear.”
The inner ear provides a unique opportunity for intervention following genetic analysis. It is accessible with very minimal risk, has anatomic boundaries that limit spread of therapeutic vectors to surrounding tissues, and can provide reliable and objective outcome measures. These interventions are not possible however, without a fundamental knowledge of the underlying mutations and understanding of the natural history of specific genetic changes.
Given the vastness of the human genome, determining the prognosis of hearing loss in adult patients will involve the creation of a comprehensive testing battery. This data will contribute to the creation of novel, specific treatments beyond those currently available to halt hearing loss or potentially cure the disorder.
The Advantage: Early Treatment for Adult-Onset Hearing Loss
Preemptive therapy is among the many advantages of identifying the causative genetic mutation in adult-onset hearing loss. Treatment options directed at the specific mutation, applied early in the course of the disease, could avoid decades of hearing rehabilitation and maintain patient quality of life. Further, early identification and intervention has the potential to prevent irreversible damage to the complex anatomic relationships necessary for proper cochlear function.
Adult-Onset Hearing Loss Team
Vice Chairman of Penn Otorhinolaryngology, Dr. Ruckenstein will be joined at the Center by fellow members of the department Drs. Douglas Bigelow, Jason Brant, Steven Eliades, Douglas Epstein and Daniel Rader, as well as audiologist, genetic counselors, and a computational genetics team.
This multidisciplinary team will identify patients likely to harbor mutations associated with progressive adult-onset hearing loss, determine their genetic risk, screen for those likely to benefit from intervention, develop therapeutics, and ultimately implement those therapies in the clinic. The Penn Center for Adult-Onset Hearing Loss is novel not only for the team involved, but also for the University, and the field at large.
The Center will also contribute to clinical research for novel treatments designed to either address the by-product of the genetic mutation or to address the mutation itself., and, because hearing loss in adults can have many etiologies, will offer a full array of audiometric testing.