SLC26A4 Gene: Hearing Loss and Pendred Syndrome Explained

The human body contains tens of thousands of genes, and one such gene, SLC26A4, holds the blueprint for a protein with specialized roles. When the instructions within this gene are altered, it can lead to health changes, particularly affecting hearing and the function of the thyroid gland. Understanding this gene is the first step in comprehending the conditions associated with it.

Understanding the SLC26A4 Gene and Pendrin Protein

The SLC26A4 gene contains the code to produce a protein named pendrin. This protein’s primary job is to transport ions like chloride, iodide, and bicarbonate across cell membranes, ensuring these particles are in the right place at the right time. This transport function is particularly active in the inner ear and the thyroid gland.

In the thyroid, a gland at the base of the neck, pendrin transports iodide, a necessary ingredient for producing thyroid hormones that regulate metabolism. In the inner ear, pendrin helps maintain the precise balance of ions in the surrounding fluid. This chemical equilibrium is necessary for the normal development and function of the structures responsible for hearing and balance.

SLC26A4 Mutations and Hearing Impairment

When the SLC26A4 gene has a mutation, it can result in a faulty or non-functional pendrin protein. This disruption has significant consequences for the inner ear, where the altered fluid balance can affect the development and health of the sensory cells needed to detect sound. These changes are a direct cause of hearing impairment.

One condition resulting from these mutations is a form of hearing loss known as DFNB4, which is not associated with symptoms in other parts of the body. Individuals with DFNB4 often have a structural difference in the inner ear called an enlarged vestibular aqueduct (EVA). The vestibular aqueduct is a small, bony canal that runs from the inner ear toward the brain, and in people with EVA, this canal is larger than usual.

The hearing loss associated with DFNB4 and EVA can be present from birth or develop after a child learns to speak. It is often progressive, meaning it can worsen over time, and an individual’s hearing ability can also fluctuate. Those with an enlarged vestibular aqueduct are more susceptible to a sudden decline in hearing following minor head trauma, as the structural vulnerability makes the inner ear more sensitive to pressure changes.

Pendred Syndrome and Its Connection to SLC26A4

Mutations in the SLC26A4 gene are also the cause of a genetic disorder called Pendred syndrome. This condition is described as syndromic because it affects multiple systems in the body. The defining characteristics of Pendred syndrome are a combination of sensorineural hearing loss and abnormalities of the thyroid gland. The hearing loss is present from early childhood and is often in the severe to profound range.

The thyroid issue most commonly associated with Pendred syndrome is the development of a goiter, an enlargement of the thyroid gland that appears in late childhood or early adolescence. While the gland is enlarged, its function may remain normal for many years, a state referred to as euthyroid. In some individuals, the thyroid may eventually become underactive, a condition known as hypothyroidism.

Both the hearing loss and the goiter in Pendred syndrome stem from the malfunctioning pendrin protein. The faulty ion transport impairs the thyroid’s ability to process iodide correctly, leading to the gland’s enlargement. Some individuals with the syndrome may also experience issues with balance because the vestibular system, which controls balance, is also affected.

Inheritance Patterns and Diagnostic Processes

The conditions linked to SLC26A4 mutations are inherited in an autosomal recessive pattern. For an individual to be affected, they must inherit two mutated copies of the SLC26A4 gene, one from each parent. The parents, who each carry only one mutated copy, are known as carriers and do not show signs of the condition.

Diagnosing these disorders involves a multi-step process.

• Comprehensive hearing evaluations, or audiological tests, to determine the type and severity of hearing loss.
• Medical imaging, such as a CT scan or MRI of the temporal bones, to visualize the inner ear and look for an enlarged vestibular aqueduct.
• Thyroid function tests and ultrasound to examine the gland’s structure if a goiter is present or Pendred syndrome is suspected.
• Molecular genetic testing of a blood sample to identify specific mutations in the SLC26A4 gene, which confirms the diagnosis.

Genetic counseling is often recommended to help families understand the diagnosis, inheritance pattern, and implications for other family members.

Managing Conditions Linked to SLC26A4

There is no treatment that can correct the underlying genetic mutation in SLC26A4, so management focuses on addressing the symptoms. For hearing loss, interventions are tailored to the person’s needs. Hearing aids can be effective for many, while cochlear implants are an option for those with more severe or profound hearing loss.

Regular monitoring by an audiologist is important to track any changes in hearing. For individuals with Pendred syndrome, periodic evaluation of the thyroid is also standard. This includes monitoring the size of a goiter and testing hormone levels to detect hypothyroidism, which can be managed with hormone replacement therapy.

Because of the inner ear’s vulnerability in people with an EVA, preventative measures are advised. Patients are often counseled to avoid contact sports or activities with a high risk of head injury. If balance problems are present, vestibular rehabilitation therapy can help individuals manage dizziness and improve stability.