Vestibular aqueducts are narrow, bony canals that travel from the inner ear to deep inside the skull (see figure). The aqueducts begin inside the temporal bone, the part of the skull just above the ear. The temporal bone also contains two sensory organs that are part of the inner ear. These organs are the cochlea, which detects sound waves and turns them into nerve signals, and the vestibular labyrinth, which detects movement and gravity. These organs, together with the nerves that send their signals to the brain, work to create normal hearing and balance. Running through each vestibular aqueduct is a fluid-filled tube called the endolymphatic duct, which connects the inner ear to a balloon-shaped structure called the endolymphatic sac.

Recent studies indicate that a vestibular aqueduct is abnormally enlarged if it is larger than one millimeter, roughly the size of the head of a pin. This is called an enlarged vestibular aqueduct, or EVA; the condition is also known as a dilated vestibular aqueduct or a large vestibular aqueduct. If a vestibular aqueduct is enlarged, the endolymphatic duct and sac usually grow large too. The functions of the endolymphatic duct and sac are not completely understood. Scientists believe that the endolymphatic duct and sac help to ensure that the fluid in the inner ear contains the correct amounts of certain chemicals called ions. Ions are needed to help start the nerve signals that send sound and balance information to the brain.

EVA has many causes, not all of which are fully understood. The most well-known cause of EVA and hearing loss is mutations in a gene called SLC26A4 (previously known as the PDS gene). Two mutations in the SLC26A4 gene can result in Pendred syndrome. Scientists believe that other, currently unknown, genetic or environmental factors also may lead to EVA.

Normal Function

The SLC26A4 gene provides instructions for making a protein called pendrin. This protein transports negatively charged particles (ions), including chloride, iodide, and bicarbonate, across cell membranes. Pendrin is produced in several organs and tissues, particularly the inner ear and thyroid gland.

The thyroid gland is a butterfly-shaped organ at the base of the neck that releases hormones to help regulate growth and the rate of chemical reactions in the body (metabolism). In the thyroid, pendrin is believed to transport iodide ions out of certain cells. Iodide is needed for the normal production of thyroid hormones.

In the inner ear, pendrin likely helps control the proper balance of ions, including chloride and bicarbonate. Maintaining the proper levels of these ions appears to be particularly important during development of the inner ear, and it may influence the shape of bony structures such as the cochlea and vestibular aqueduct. The cochlea is a snail-shaped structure that helps process sound. The vestibular aqueduct is a bony canal that connects the inner ear with the inside of the skull.

Pendrin is also found in other tissues, including the kidneys, liver, and lining of the airways. Researchers are studying the role of pendrin's ion transport function in these tissues.

Health Conditions Related to Genetic Changes

Congenital hypothyroidism

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Nonsyndromic hearing loss

Dozens of SLC26A4 gene mutations have been identified in people with nonsyndromic hearing loss, which is loss of hearing that is not associated with signs and symptoms affecting other parts of the body. Mutations in this gene cause a form of nonsyndromic hearing loss called DFNB4. This form of hearing loss can either be present before a child learns to speak (prelingual) or begin after a child learns to speak (postlingual). Most people with DFNB4 also have an unusually large vestibular aqueduct (enlarged vestibular aqueduct, or EVA).

Mutations in the SLC26A4 gene impair or eliminate the activity of pendrin, which upsets the balance of ions in the inner ear. These changes presumably affect the development of structures in the inner ear, including the cochlea and vestibular aqueduct. Studies suggest that the changes in ion levels also lead to the loss of sensory cells in the inner ear that are needed for hearing.

Pendred syndrome

Researchers have identified more than 150 mutations in the SLC26A4 gene in people with Pendred syndrome. This condition is characterized by enlargement of the thyroid gland (called a goiter), hearing loss, and other abnormalities of the inner ear, including an enlarged vestibular aqueduct.

Some of the SLC26A4 gene mutations change single protein building blocks (amino acids) used to make pendrin. Other mutations add or delete a small amount of DNA in the SLC26A4 gene. All of these genetic changes impair or eliminate the activity of pendrin, which disrupts ion transport. In the thyroid, the disrupted ion transport prevents iodide ions from being available for thyroid hormone production. To compensate for the perceived lack of iodide, the thyroid tissue enlarges to form a goiter. In the inner ear, impaired pendrin activity alters the balance of ions, which presumably affects the development of structures including the cochlea and vestibular aqueduct. Studies suggest that the changes in ion levels also lead to the loss of sensory cells in the inner ear that are needed for hearing.

Because their signs and symptoms overlap, it can be difficult to distinguish Pendred syndrome from nonsyndromic hearing loss (DFNB4, described above). Many of the SLC26A4 gene mutations associated with Pendred syndrome have also been found to cause DFNB4. Mutations in this gene can also cause other thyroid abnormalities; in a small number of people, SLC26A4 gene mutations have been associated with an abnormally small thyroid gland (thyroid hypoplasia) that causes a loss of thyroid function from birth (congenital hypothyroidism). It is unclear whether Pendred syndrome, DFNB4, and thyroid hypoplasia caused by SLC26A4 gene mutations are best considered as separate disorders or as a spectrum of related signs and symptoms.

Age-related hearing loss

MedlinePlus Genetics provides information about Age-related hearing loss

Hashimoto's disease

MedlinePlus Genetics provides information about Hashimoto's disease

Other Names for This Gene

• PDS
• pendrin
• S26A4_HUMAN
• solute carrier family 26 (anion exchanger), member 4
• solute carrier family 26, member 4

Genomic Location

Genes are the means by which we inherit traits and disorders from our parents. Genes provide instructions to our cells to determine how we grow and develop in the womb and after we are born.

We have a pair of each gene for every trait we inherit. A child inherits one copy of most genes from the mother and another copy from the father. This happens when the egg and sperm come together at conception. Research from the Human Genome Project suggests that humans have between 20,000 and 25,000 pairs of genes in every cell of their bodies!

Chances of Inheriting a Recessive Disorder

Genetic disorders can be caused by a change(s) in a gene. Every individual has two copies of the same gene. Genetic disorders are inherited in different ways.

Recessive means:

• a person must inherit a change in the same gene from each parent in order to have the disorder
• a person with one changed gene does not have the disorder, but can pass either the changed or the unchanged gene on to his or her child

An individual with the disorder usually:

• has inherited a change in the same gene from each parent

An individual who has one changed gene is called a carrier. When two carriers of the same changed gene have a child together, with each birth there is a:

• 1 in 4 chance of having a child with the disorder
• 2 in 4 chance of having a child who is a carrier
• 1 in 4 chance of having a child who neither has the disorder nor is a carrier

Mutations

Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different among people. These changes in a gene are often called mutations. Many of these mutations cause us no problems at all. For example, they may explain why you have blue eyes but your brother has brown—or why your best friend in high school could run very fast, while you were good at math.

Some changes in genes, though, can cause medical problems and disorders. Changes in a gene can result in a person’s blood not clotting properly or cause weak, brittle bones. Changes in more than 100 different identified genes can cause hearing loss.

Inheritance

Most genetic disorders are inherited in an autosomal manner. Autosomal means that men and women are equally likely to have the disorder and equally likely to pass it on to a child of either sex. Disorders can also be inherited in a sex-linked manner. For most sex-linked traits, women rarely have the trait, and they pass it on only to their sons.

Sometimes a mutation in only one copy of a gene can cause a medical disorder. If this is the case, the trait is said to be inherited in a dominant manner. A recessive disorder, on the other hand, arises only when the mutation occurs in both copies of the gene. Hearing loss can be inherited in a dominant or recessive manner, depending on the gene that is causing the hearing loss.

A person with one change in a gene that is responsible for an autosomal recessive disorder typically has no signs or symptoms of the disorder. These individuals are often referred to as carriers, because they "carry" a mutation but are not affected by it. Usually when an individual has a recessively inherited disorder, both parents are carriers of a gene mutation for the disorder.

EVA

In an ongoing study by NIDCD scientists of more than 100 patients, approximately one-fourth of individuals with EVA and hearing loss were diagnosed with Pendred syndrome. Pendred syndrome is inherited in a traditional autosomal recessive manner as described above. It is the result of two mutations in the SLC26A4 gene.

One-fourth of the study volunteers had one mutation in SLC26A4. Recent research has shown these families have a similar inheritance pattern to those families with two mutations. This suggests that there may be another mutation in the gene that was not detected. The NIDCD researchers are continuing to study this “missing mutation.”

The remaining half of the NIDCD study volunteers had no mutations in SLC26A4. Scientists are continuing to seek other genes that may be responsible for EVA and hearing loss.

Research suggests that most children with enlarged vestibular aqueducts (EVA) will develop some amount of hearing loss. Scientists also are finding that 5 to 15 percent of children with sensorineural hearing loss (hearing loss caused by damage to sensory cells inside the cochlea) have EVA. However, scientists do not think that EVA causes the hearing loss, but that both are caused by the same underlying defect. EVA can be an important clue pointing to what is actually causing the hearing loss.

EVA can be a sign of a genetic disorder called Pendred syndrome, a cause of childhood hearing loss. According to a study by the National Institute on Deafness and Other Communication Disorders (NIDCD), approximately one-fourth of the people with EVA and hearing loss have Pendred syndrome. Hearing loss associated with Pendred syndrome is usually progressive, which means that a child will lose hearing over time. Some children may become totally deaf.

In addition to its association with hearing loss, EVA also may be linked to balance problems in a small percentage of people. However, the brain is very good at making up for a weak vestibular system, and most children and adults with EVA don't have balance disorders or difficulty doing routine tasks.

Medical professionals use different clues to help them determine the cause of hearing loss. Two tests that are often used to identify the cause of hearing loss are magnetic resonance imaging (MRI) and computed tomography (CT) imaging of the inner ear. One or both tests are often recommended to evaluate a child with sensorineural hearing loss. This is particularly true when a child's hearing loss occurs suddenly, is greater in one ear than the other, or varies or gets worse over time. Although most CT scans of children with hearing loss are normal, EVA is the most commonly observed abnormality.

No treatment has proven effective in reducing the hearing loss associated with EVA or in slowing its progression. Although some otolaryngologists (a doctor or surgeon who specializes in diseases of the ears, nose, throat, and head and neck) recommend steroids to treat sudden sensorineural hearing loss, there are no scientific studies to show that this is an effective treatment for EVA. In addition, surgery to drain liquid out of the endolymphatic duct and sac or to remove the endolymphatic duct and sac is not only ineffective in treating EVA, it can be harmful. Research has shown conclusively that these surgeries can destroy hearing.

To reduce the likelihood of progression of hearing loss, people with EVA should avoid contact sports that might lead to head injury; wear head protection when engaged in activities such as bicycle riding or skiing that might lead to head injury; and avoid situations that can lead to barotrauma (extreme, rapid changes in air pressure), such as scuba diving or hyperbaric oxygen treatment. The pressure changes associated with flying in airplanes have also been reported to cause hearing loss in people with EVA. However, this is a rare event in commercial aircraft with pressurized cabins. If you have EVA, you can minimize your risk of hearing loss associated with air travel by taking nasal decongestants if you have sinus or nasal congestion, such as during a cold or flu.

Identifying hearing loss as early as possible is the best way to reduce EVA's impact. The earlier hearing loss is identified in children, the sooner they can develop skills that will help them learn and communicate with others. Children with permanent and progressive hearing loss, which is often linked with EVA, will benefit from learning other forms of communication, such as sign language or cued speech, or using assistive devices, such as a hearing aid or cochlear implant.

While mutations in the SLC26A4 gene are known to cause EVA, not all EVA cases are the result of an SLC26A4 mutation. Some cases may be caused by other genetic or environmental factors. For these reasons, NIDCD researchers are currently conducting a clinical study to identify and understand the various factors that can lead to EVA and hearing loss. More information on this study is available here.