Genetic diagnosis can play an important role in guiding the care of childhood hearing loss. Genetic testing can help determine the cause of the hearing loss and inform the appropriate medical management and treatment options. This information can also inform genetic counseling for families, helps predict future hearing loss in other family members, and potentially inform the development of new treatments.
Advances in understanding the numerous genetic causes of childhood-onset hearing loss suggest that genomic testing could aid in individualizing treatment planning, including treatment timing. According to new research, genetic testing can help determine a child’s hearing loss prognosis and predict how useful a cochlear implant might be for that child’s speech understanding. It is possible to predict future hearing loss across sound frequencies, progression with age, and severity using genetic diagnosis.
Advances in understanding the many different genetic causes of childhood-onset hearing loss suggest that genomic testing could help with treatment planning, including optimal treatment timing. Even if a child with hearing loss did not receive a diagnosis from genetic testing a few years ago, scientists in this field say that the very rapid recent progress in genomics makes re-testing worthwhile.
Hearing loss, which is usually caused by sensory problems in the inner ear, affects about one in every 400 newborns in the United States. Half of these children have hearing loss due to a genetic condition. Childhood hearing loss can be caused by more than 120 genes and thousands of different genetic variants. Almost all children with genetic hearing loss have a single gene mutation or mutations.
With genetic diagnosis, it is possible to anticipate future hearing loss across sound frequencies and progression with age. This information can be integrated with current severity of hearing loss to decide on treatment.
Ryan J. Carlson
A recent study published in JAMA Otolaryngology-Head & Neck Surgery looked at over 400 children who had bilateral sensorineural hearing loss in both ears.
The researchers from UW Medicine and Seattle Children’s Hospital set out to discover the genetic causes of hearing loss in this population, as well as how each genetic cause relates to a specific type of hearing loss. They also looked into whether the genetic cause of hearing loss was linked to the success of treatment with a cochlear implant, which is a surgically implanted electronic device that allows a person to sense sound by sending impulses to the brain.
The findings show that genetic testing is a valuable tool in determining prognosis for a child’s hearing loss and in predicting how useful a cochlear implant could be for that child’s understanding of speech.
“With genetic diagnosis, it is possible to anticipate future hearing loss across sound frequencies and progression with age,” the researchers noted in their paper. “This information can be integrated with current severity of hearing loss to decide on treatment.”
The study was led by Ryan J. Carlson, an M.D./Ph.D. student in the Medical Scientist Training Program at the University of Washington School of Medicine in Seattle.
“Genomic testing can now identify a genetic cause for more than half of pediatric patients’ hearing loss and often provide critical information on its clinical characteristics,” Carlson explained.
Participants in the study included 449 children from 406 families. 210 of the 406 families had genetic diagnoses as a result of genomic analysis, including 55 of the 82 families with more than one child with hearing loss and 155 of the 324 families with a single child with hearing loss. All ancestries in the study group had similar rates of genetic diagnosis.
The researchers discovered hearing loss-causing variants in 43 different genes in this study population. With one exception, each child’s genetic diagnosis involved only one gene. The severity of hearing loss, the sound frequencies most affected, and changes in hearing loss over time varied by gene and, in some cases, by the type of variant within the gene. Children with causative mutations in the genes MYO6, OTOA, SLC2644, TMPRSS3, or the most severe mutations in the GJB2 gene had progressive hearing loss.
All of the children who received cochlear implants had better speech perception than before they received their implants. The degree of success of the cochlear implant varied depending on the participant’s genetic diagnosis.
Taking into account the age of the child at implant and the length of time the implant was in place, speech perception was highest for children whose hearing loss was due to mutations in the MITF or TMPRSS3 genes.
However, the researchers concluded that differences in success of cochlear implants related to the genetic diagnosis was not substantial enough to preclude a cochlear implant for any patient who otherwise met the implant criteria.
Ancestries of the study participants were 17 (4%) African/African American, 32 (8%) East Asian, 219 (54%) European, 53 (13%) Latinx, 16 (4%) South Asian, and 61 (15%) who reported more than one ancestry. Slightly more than half (51%) of the children in the study were female
The research was carried out at the otolaryngology and audiology clinics at Seattle Children’s Hospital and the University of Washington, including the Center for Human Development and Disability, from 2019 to 2022.
In Mary-Claire King’s genome sciences laboratory at the University of Washington School of Medicine, DNA from participants was analyzed using genomic sequencing and structural variant analysis. Audiological testing was used to assess the severity and progression of their hearing loss, and pediatric or adult speech perception testing was used to assess the success of their cochlear implant.
The research team outlined several key conclusions from their findings:
In most pediatric patients, genetic testing for hearing loss can identify a genetic cause. Because hearing loss is not detectable at birth, newborn hearing screening misses about one-third of affected children. That chasm could be bridged by genetic testing. Second, genomic analysis technologies are rapidly improving. If a child has already had genetic testing and received negative results, re-testing may reveal a previously missed genetic cause. Third, genetic testing can identify syndromic forms of hearing loss, allowing children to be referred to key specialists.
Finally, genetic diagnoses can be used to inform precision treatment for childhood hearing loss more effectively. Once the clinical characteristics of a specific genetic cause are known, that information can be used to assess prognosis and guide treatment. “Detection of hearing loss at the earliest possible age is important for cognition and social development, regardless of management approach,” the researchers concluded.
Carlson stated that the study directly benefited its participants. “In this single study, we were able to provide genetic testing for over 400 families with hearing loss. Many participants received new genetic diagnoses that were critical to their treatment “He elaborated. “I am proud to have directed a project that provided both direct and indirect benefits to those involved as well as all patients with hearing loss.”
