The Pendred Syndrome Gene and Its Effects on the Body

Pendred syndrome is a genetic condition that primarily affects the inner ear and the thyroid gland, leading to hearing loss and, in many cases, an enlargement of the thyroid known as a goiter. First described in 1896, this disorder can also impact balance. The symptoms and their severity can vary significantly among individuals, making its presentation complex. The condition stems from an inherited genetic change that disrupts the function of a specific protein involved in ion transport.

Genetic Causes of Pendred Syndrome

Pendred syndrome is an autosomal recessive disorder, meaning an individual must inherit two copies of a mutated gene—one from each parent—to develop the condition. The gene most commonly responsible is SLC26A4, located on chromosome 7, which holds the instructions for building a protein called pendrin. The pendrin protein acts as a transporter, moving ions like chloride, iodide, and bicarbonate across cell membranes in the inner ear, thyroid gland, and kidneys.

Mutations in the SLC26A4 gene lead to a dysfunctional pendrin protein or prevent its production, disrupting ion transport. The severity and combination of symptoms can differ based on the specific mutations. While SLC26A4 mutations are the primary cause, changes in other genes, such as FOXI1 and KCNJ10, have been associated with the syndrome in a smaller number of cases.

This genetic basis explains its variable expression, where even family members with identical mutations may experience different health issues. Genetic counseling is often recommended for families to understand the inheritance pattern and the likelihood of passing the condition to future children.

How Pendred Syndrome Affects the Body

In the inner ear, pendrin helps maintain the fluid and ion balance necessary for hearing and balance. When this function is impaired, it often leads to structural changes, such as an enlarged vestibular aqueduct (EVA). These abnormalities contribute to sensorineural hearing loss that is present from birth or develops in early childhood. The hearing loss is in both ears and can worsen over time, sometimes progressing after minor head injuries.

In addition to hearing loss, vestibular or balance problems affect a majority of individuals with Pendred syndrome. The disruption of the inner ear’s structures can lead to feelings of dizziness or unsteadiness.

The thyroid gland is also affected. Pendrin plays a role in transporting iodide into thyroid cells for the production of thyroid hormones. Although this process is partially impaired, many individuals maintain normal thyroid hormone levels. The gland often enlarges to compensate, forming a goiter that appears in late childhood or adolescence. In some cases, the thyroid may become underactive (hypothyroidism), which requires medical treatment.

Diagnosing Pendred Syndrome

Diagnosing Pendred syndrome requires evaluation by a multidisciplinary team, often including an otolaryngologist, audiologist, endocrinologist, and geneticist. The process begins with a clinical assessment based on hearing loss and, if present, a goiter. Audiological testing confirms the presence and extent of sensorineural hearing loss, and tests like otoacoustic emissions (OAE) and auditory brainstem response (ABR) are used to evaluate inner ear function.

Imaging studies such as a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the inner ear can reveal structural abnormalities. The most common finding is an enlarged vestibular aqueduct (EVA), but other malformations like an atypical cochlea may also be seen. These anatomical markers are strong indicators of the syndrome.

To evaluate the thyroid, physicians use an ultrasound to examine the gland’s size and structure, along with blood tests to measure hormone levels. The definitive confirmation of Pendred syndrome comes from genetic testing. A blood test can identify mutations in the SLC26A4 gene, which is considered the standard for diagnosis.

Approaches to Managing Pendred Syndrome

There is no cure for Pendred syndrome, so treatment focuses on managing specific symptoms, with early intervention for hearing loss as a primary goal. Management strategies include hearing aids to amplify sound for those with mild to moderate hearing loss. For individuals with severe to profound hearing loss, cochlear implants are an effective option that bypasses damaged parts of the inner ear to directly stimulate the auditory nerve. Educational support and learning sign language are also valuable tools for communication.

The thyroid-related aspects of the syndrome require regular monitoring by an endocrinologist, who checks the goiter size and hormone levels. If an individual develops hypothyroidism, treatment with thyroid hormone replacement therapy is initiated. Surgery to remove the goiter is rarely needed unless it becomes very large and causes compressive symptoms.

For individuals experiencing balance problems, vestibular rehabilitation therapy can be beneficial. This physical therapy helps the brain adapt to abnormal signals from the inner ear, improving stability and reducing dizziness. Because the features of Pendred syndrome can change over time, lifelong follow-up with a coordinated team of specialists is necessary to address new issues promptly.