by Neil Bauman, Ph.D.
© July, 2019
You may have thought that most hearing loss is caused by hair cells dying. You would have been right if you were just thinking about hearing loss due to exposing your ears to loud noises. At the same time, you’d be mostly wrong if you ignored all the other kinds of hearing losses, especially the numerous kinds of genetic hearing losses.
Likely you have heard about the Connexin 26 mutation of the GJB2 gene—the most common known cause of congenital sensorineural hearing loss. But that is only one of hundreds of genes/genetic mutations known to affect hearing.
Up to now, researchers have discovered a whopping 400 genes that can affect hearing in humans. However, by extrapolating from what they know about genes that cause hearing loss in mice, they think that there are yet still another 600 genes involved in auditory function in humans that remain to be found. (1) This suggests that there are at least 1,000 different genes that can affect hearing in humans.
According to professor Karen Steel, Ph.D., researchers can make this prediction because, “despite the difference in the size of the inner ear and the spectrum of frequencies detected, there are remarkable similarities in the anatomy, physiology, genetics, and pathology of the auditory system in mice and humans”. (1)
Recently, researchers have discovered another 38 genetic mutations in mice that cause hearing loss. Of these new mutations, they found that numbers of the mutations had normal auditory brainstem response thresholds but abnormal waveforms. This may correlate with the finding that many people report difficulty hearing in noisy environments, but when tested, have normal audiograms. (1)
By analyzing these various genetic mutations in mice, researchers have realized that there are a wide range of underlying pathologies that can lead to hearing loss and that a large number of different genes likely are involved.
Of the 38 genes mentioned above, all suggest that similar genes in people will cause hearing losses also. In fact, they have already “found evidence that two of these mouse genes are also mutated in human families with inherited deafness”. (1)
Obviously, there are an enormous number of different kinds of hearing losses caused by genetic mutations in these many different genes! It should be no surprise then, that some of these genetic mutations result in profound hearing loss, while others only show a mild hearing loss of perhaps 20 dB or so. Some cause hearing loss across all or most frequencies, and other only result in hearing loss at certain frequencies.
For instance, some hearing losses are in the high frequencies (the typical ski-slope hearing loss). Others are low-frequency losses (the rare reverse-slope hearing loss). Still others are flat losses (roughly the same hearing loss at all frequencies).
Furthermore, these various hearing losses arise from different underlying pathologies. For example, several genes were associated with conductive hearing loss due to middle ear inflammation. Other mutations cause such things as abnormal inner hair cells and defects of inner and outer hair cells. Still other mutations result in flaws in the synapses that transmit signals from the hair cells to the auditory nerve. In addition, some genetic mutations result in reduced endocochlear potentials—think of the cochlear “battery” as half run down.
Obviously, you no longer can assume that all hearing loss is due to hair cells dying. This is just not true. Each of the above conditions come from very different causes—but all are ultimately from specific genetic defects.
It’s interesting that some of these genetic mutations caused hearing loss from childhood through old age. However, many of them show normal childhood auditory brainstem responses (ABR) followed by progressive hearing loss as the person gets older.
It would be great if ear specialists could develop better diagnostic techniques so they can tell exactly where and from what the hearing loss developed.
For example, they already know that people with the GJB2 genetic mutation have excellent results when they have cochlear implants. They also know that people with genetic mutations that affect the cochlear nerve do not do as well with cochlear implants. (2)
They also know that people with the A1555G variant of the 12S rRNA gene are very susceptible to hearing loss from taking any of the aminoglycoside antibiotics. (3)
Perhaps one day soon they will find exactly which genes cause Large Vestibular Aqueduct Syndrome (LVAS/EVAS). They already know of two “marker” genes, but not the specific genes that actually cause the hearing loss.
Also, I wouldn’t mind knowing the genetic origin of the extreme reverse-slope hearing loss that runs in my family.
(1) Steel, Karen. 2019. Lessons about Hearing Loss from Mice. Hearing Journal, Vol. 72, No. 7, July 2019, p 6.
(2) Decoding Genes. In: Hearing Health. Hearing Health Foundation. Summer 2019. p. 20.
(3) Bauman, Neil. 2010. Genetics and Aminoglycoside Ototoxicity. In: Ototoxic Drugs Exposed. Integrity First Publications. Lynden, WA.