Before we can explain genetic hearing loss it is important to understand how humans hear.
How do we hear?1
Hearing depends on a series of events that change sound waves in the air into electrical signals. Your auditory nerve then carries these signals to your brain through a complex series of steps.
1. Sound waves enter the outer ear and travel through a narrow passageway called the ear canal, which leads to the eardrum.
2. The eardrum vibrates from the incoming sound waves and sends these vibrations to three tiny bones in the middle ear. These bones are called the malleus, incus, and stapes.
3. The bones in the middle ear couple the sound vibrations from the air to fluid vibrations in the cochlea of the inner ear, which is shaped like a snail and filled with fluid. An elastic partition runs from the beginning to the end of the cochlea, splitting it into an upper and lower part. This partition is called the basilar membrane because it serves as the base, or ground floor, on which key hearing structures sit.
4. Once the vibrations cause the fluid inside the cochlea to ripple, a traveling wave forms along the basilar membrane. Hair cells, sensory cells sitting on top of the basilar membrane, ride the wave.
5. As the hair cells move up and down, microscopic hair-like projections (known as stereocilia) that perch on top of the hair cells bump against an overlying structure and bend. Bending causes pore-like channels, which are at the tips of the stereocilia, to open up. When that happens, chemicals rush into the cells, creating an electrical signal
6. The auditory nerve carries this electrical signal to the brain, which turns it into a sound that we recognize and understand.
Photo Credit: Stereocilia perch atop sensory hair cells in the cochlea of the inner ear Credit: Yoshiyuki Kawashima
Genetic Hearing Loss2
Hearing loss is the most familiar sensory defect present in humans, affecting more than 10 percent of people age 65 and older. In many cases, hearing loss is caused by multiple factors, including genetic and environmental causes. Single-gene mutations can often lead to hearing loss. Genetic factors make some people more susceptible to hearing loss as their genes make them more predisposed due to ageing, loud noises, infections, or drugs. It is estimated that between 30 and 60 percent of age-related hearing loss is due to genetics.
Sensorineural Hearing Loss and Conductive Hearing Loss
There are two primary forms of hearing loss. These include sensorineural hearing loss and conductive hearing loss – as well as a combination of the two. Sensorineural hearing loss begins when there is harm done to the cochlea inner ear or to nerve pathways that run from the inner ear to the brain. Sensorineural hearing loss reduces the ability to hear faint sounds. Common causes include illnesses, aging, certain drugs, genetics, head trauma, malformation of the inner ear, and loud noises.
Conductive hearing loss is caused when sound is not properly conducted through the outer ear and into the eardrum. Common conductive hearing loss causes include allergies, ear infection, benign tumors, and infection in the ear canal, impacted eardrum, swimmer’s ear, or presence of a foreign object.
Hearing Loss & Genetics: Understanding the Basics. A PowerPoint slide by Anna Frangulov, B.S. Research Coordinator Children’s Hospital Boston
Syndromic Versus Non-Syndromic2
Genetics is one of the most common hearing loss causes, accounting for approximately 60 percent of deafness occurring in infants. An average of three in every 1,000 babies is born with hearing loss or born deaf. Genetics is also one of the leading hearing loss causes in the elderly. Inherited genetic defects can occur at any point in a person’s life, leading to sudden hearing loss. These same defects can also cause a person to become deaf.
Syndromic: Syndromic refers to a hearing impairment associated with clinical abnormalities. Out of all genetic-related hearing loss, syndromic makes up 15 to 30 percent. More than 400 syndromes are known to include some type of hearing problem. These can include syndromes transmitted in Mendelian or monogenic, syndromes due to chromosomal anomalies, syndromes due to multi-factorial influences, or syndromes due to a combination of these.
Non-Syndromic: Non-syndromic refers to a hearing impairment that accounts for the majority of genetic-related hearing loss, nearly 70 percent. Autosomal-dominant genes account for up to 20 percent while autosomal-recessive inheritance is responsible for more than 80 percent of non-syndromic cases. Less than two percent of all cases are caused by mitochondrial genetic and X-linked malfunctions.
– Prelingual hearing loss is present before speech develops. All congenital (present at birth) hearing loss is prelingual, but not all prelingual hearing loss is congenital.
– Postlingual hearing loss occurs after the development of normal speech.
The different gene loci for nonsyndromic deafness are designated DFN (for DeaFNess). Loci are named based on mode of inheritance:
– DFNA: Autosomal dominant
– DFNB: Autosomal recessive
– DFNX: X-linked
Examples of clinical manifestations and molecular genetics of known genes causing hearing impairment
1. The auditory system. NIH/NIDCD website accessed June 2017 (https://www.nidcd.nih.gov/health/age-related-hearing-loss)
2. Genetic Hearing Loss. Deaf Websites website accessed June 2017 (http://www.deafwebsites.com/hearing-loss/genetic-hearing-loss.html)
3. Deafness and Hereditary Hearing Loss Overview. Authors: Smith RJH, Shearer AE, Hildebrand MS, Van Camp G. Editors: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K. Source: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. 1999 Feb 14 [updated 2014 Jan 9]. (https://www.ncbi.nlm.nih.gov/books/NBK1434/)