What is Pendred Syndrome?
Pendred syndrome is a health condition that usually manifests with two key symptoms: sensorineural hearing loss, or loss of hearing caused by damage to the inner ear, and a thyroid goiter, which is an enlarged thyroid gland. In some instances, people with this syndrome may also suffer from hypothyroidism, a condition in which the thyroid doesn’t produce enough hormones. Pendred syndrome is a genetic disorder, which means it is inherited, needing faulty mutations from both parents in a gene known as PDS. The reason for these health problems is due to a flaw in a protein called pendrin, which is caused by this faulty gene.
What Causes Pendred Syndrome?
Pendred syndrome happens because of changes in a particular gene known as The Pendrin Gene (PDS/SLC26A4). This gene is responsible for making a protein called Pendrin/SLC26A4. This gene is located on a specific area of chromosome 7 (known as 7q22.3), and it’s active in several parts of the body, including the inner ear, kidneys, thyroid, and cells lining the airways in the lungs.
The Pendrin/SLC26A4 protein is like a multi-purpose transporter that can move different types of particles (specifically, negatively charged particles called anions) around in your body. It has a particular liking for chloride, iodide, bicarbonate, and other similar particles.
Risk Factors and Frequency for Pendred Syndrome
Pendred syndrome, a condition that frequently results in deafness from birth, affects an estimated 7.5 to 10 individuals per 100,000. It’s responsible for up to 10% of congenital deafness cases, making it potentially the most common reason behind hearing loss tied to a specific condition or syndrome. As it’s inherited in an ‘autosomal recessive’ manner, there’s a 25% risk of a child getting the disease if both parents carry the gene.
Signs and Symptoms of Pendred Syndrome
Pendred syndrome can affect several parts of the body, including hearing, balance, thyroid function, and the renal system.
One of the main features of Pendred syndrome is hearing loss. This is often present from birth or develops early in life, and gets worse over time. Some people’s hearing loss may be worsened further by exposure to loud noise, sudden pressure changes (barotraumas), or head injuries. Symptoms often affect both ears, but can sometimes be worse in one ear. Early signs of hearing loss include not responding to sounds and a delay in starting to speak.
Some people with Pendred syndrome may also have problems with their balance. These are not usually noticeable, but may become apparent during activities that require motor skills and balance, or when a person’s hearing starts to deteriorate. Some people may have abnormalities of the bones in the ear (temporal bone abnormalities).
- Hearing loss that can range from mild to severe
- Balance problems
- Temporal bone abnormalities
Another feature of Pendred syndrome is an enlarged thyroid gland, also known as a goiter. This happens because the body has problems using iodine, an element that the thyroid gland uses to make hormones. Some people may develop a goiter later in life. Around 75% of people with Pendred syndrome have a goiter. An adequate intake of iodine can sometimes prevent the thyroid gland from becoming enlarged.
Although the use of iodine is not completely dependent on the presence of pendrin, the protein that is faulty in Pendred syndrome, patients usually have a partial inability to use iodine. Half of people with Pendred syndrome have normal thyroid function, but some may have subclinical hypothyroidism, which can be present from birth.
- Enlarged thyroid gland (goiter)
- Problems using iodine
- Normal or low thyroid function
Abnormalities in the renal system, or kidneys, can also occur in Pendred syndrome. This can sometimes lead to potentially life-threatening metabolic alkalosis due to an imbalance in the body’s levels of acid and alkali.
- Potential for life-threatening metabolic alkalosis
Testing for Pendred Syndrome
Genetic testing is an important tool in diagnosing Pendred syndrome, a genetic disorder that affects the ears and thyroid gland. The most common gene impacted in Pendred syndrome patients is SLC26A4. About half of the people with this syndrome have a mutation in this specific gene. Other genes, like FOXII and KCNJI0, are affected in fewer than 2% of patients.
Doctors use a method called “direct sequencing” to check for specific changes in this gene. This allows them to either find two disease-causing variants of the gene, or demonstrate the presence of one disease-causing variant along with another one carried. There are many different possible mutations in the SLC26A4 gene, with about 200 variants identified so far.
However, because of the variety of possible mutations, doctors also look for certain signs and symptoms before they order these detailed genetic tests. This includes comparing a patient’s symptoms to the well-known characteristics of Pendred syndrome.
Besides genetic testing, certain imaging tests can also help make the diagnosis. A CT scan of the “temporal bone” (the bone around your ear) can reveal abnormalities often seen in patients with Pendred syndrome. Doctors measure a part of the ear called the “vestibular aqueduct,” and if it’s wider than 1.5 mm, it can support a diagnosis of Pendred syndrome. A CT scan can also reveal if the cochlea (the spiral cavity in the inner ear) has fewer than the normal 2.75 turns. If the patient has both of these findings, doctors may refer to it as “Mondini malformation.”
Pendred syndrome also affects the thyroid gland, leading to a condition called “euthyroid goiter” where the gland becomes enlarged but still makes the right amount of thyroid hormones. Doctors can use an ultrasound to give a clearer picture of the size and structure of the gland. Patients with Pendred syndrome should have regular thyroid hormone tests as well. Sometimes Pendred syndrome can coexist with autoimmune thyroiditis, a condition where the immune system attacks the thyroid gland.
Lastly, doctors may perform a perchlorate test, a specialized procedure to assess the thyroid gland’s ability to use iodine in making thyroid hormones. They do this by giving the patient a dose of radioactive iodine and then measuring what percentage is used by the thyroid gland. A low percentage (<10%) indicates a defect in this process. However, if the perchlorate test is negative, it doesn't mean the patient can't have Pendred syndrome. Many factors, including a high-iodine diet, can affect the test results.
Treatment Options for Pendred Syndrome
There isn’t a set treatment for Pendred syndrome, a genetic disorder that affects the ears and thyroid. How it’s managed depends on the specific symptoms each person displays. This usually requires a team of various healthcare professionals, including ear, nose, and throat specialists; endocrinologists (hormone doctors); geneticists; and surgeons.
One common symptom of Pendred syndrome is hearing loss. If this occurs, devices like hearing aids, which amplify sounds, or cochlear implants – devices that are surgically implanted in the ear to help provide a sense of sound, may be useful.
The thyroid, a small gland in your neck that produces important hormones, might also be affected by Pendred syndrome. Healthcare professionals will need to monitor both its function (how well it’s releasing these hormones) and its size. If there are any issues, medication or even surgery might be necessary to treat them.
Finally, since Pendred syndrome is a genetic disorder, meaning it can be passed down from parent to child, genetic counseling is an important part of managing the condition. This is a service that provides information and support to people who have or might be at risk for genetic disorders. Family members may be tested to see if they are carriers of the gene that causes Pendred syndrome, and potential risks to future children can be discussed.
What else can Pendred Syndrome be?
When diagnosing hearing loss or thyroid disease, doctors must consider other possible reasons for the symptoms. These can include:
- Non-syndromic causes of congenital deafness, which could be due to congenital infections like CMV, exposure to harmful substances, or physical injury
- Nonsyndromic enlarged vestibular aqueduct without associated thyroid issues
- Congenital hypothyroidism with hearing loss
There are also syndromes that can cause deafness such as:
- Branchiootorenal (BOR) syndrome, which involves branchial cyst, hearing loss, and kidney problems
- Waardenburg syndrome, which can cause changes in skin and hair pigment
- Usher syndrome, which is associated with retinitis pigmentosa, a type of visual impairment
- Alport syndrome, which includes hearing loss, kidney problems, and eye issues
- Jervell and Lange-Nielsen syndrome, which can result in erratic heart rhythms
- Perrault syndrome, which is known for progressive hearing loss and potential ovarian issues in women
What to expect with Pendred Syndrome
People with Pendred syndrome typically experience a gradual loss of hearing. One way to improve their hearing is through a surgery called cochlear implantation. This surgery, which involves implanting a device in the ear that provides improved hearing, can be particularly beneficial for these individuals. However, it can also be a bit more complicated due to the abnormal structure of the inner ear often seen in people with Pendred syndrome.
Additionally, Pendred syndrome can impact the thyroid gland, an organ in your neck that helps regulate your body’s energy and metabolism. This can result in a condition called euthyroid goiter, where the thyroid enlarges but continues to function normally, or clinical hypothyroidism, a condition where the thyroid doesn’t produce enough thyroid hormone leading to symptoms like fatigue, weight gain, and depression.
Possible Complications When Diagnosed with Pendred Syndrome
- Gradual loss of hearing
- Problems with the thyroid gland, such as underactive thyroid, noncancerous growths in the thyroid, or growths on the thyroid that don’t affect its function
- Severe shift in body’s acid/base balance towards too much alkali, which can be life-threatening
- There’s a rare instance of a condition called Hoffmann syndrome in association with these symptoms.
Preventing Pendred Syndrome
It’s crucial for patients to have regular check-ups for hearing and thyroid health. Regular monitoring allows doctors to catch any changes early and respond quickly if necessary. Also, it’s key to pursue genetic counseling and get family members tested too. This process can provide a clearer understanding of the potential genetic risks that may affect you, your children, or other family members.