On this page
Pendred syndrome
This inherited condition affects the inner ear's development and function, leading to hearing impairment that is usually present from birth or early childhood. Some people with Pendred syndrome may also develop thyroid issues later in life.
Available at Jeen Health
Clinical tests that include this
Overview
Pendred syndrome is a genetic disorder primarily affecting hearing and, in some cases, thyroid function. It is one of the most common causes of syndromic hearing loss, meaning hearing loss that occurs with other specific features [PMID:33678077]. Individuals with Pendred syndrome typically experience hearing loss that is present from birth (congenital) or develops early in childhood. The hearing loss is sensorineural, meaning it involves damage to the inner ear or the nerve pathways to the brain.
Beyond hearing impairment, some people with Pendred syndrome may develop an enlarged thyroid gland, known as a goitre. This usually appears later in childhood or adolescence and can sometimes be associated with mild thyroid dysfunction, though severe thyroid hormone deficiency is rare. The exact prevalence of Pendred syndrome is not well established, but it is estimated to account for a significant percentage of bilateral sensorineural hearing loss cases, particularly those with inner ear malformations.
Symptoms & clinical features
The primary symptom of Pendred syndrome is hearing loss, which is typically bilateral (affecting both ears) and sensorineural. The severity of hearing loss can vary significantly, ranging from moderate to profound, and may sometimes fluctuate [PMID:33678077]. It is often present from birth or develops in early childhood, impacting speech and language development if not identified and managed early.
Some individuals with Pendred syndrome may also experience balance problems, as the inner ear also plays a role in balance. Another key feature that may develop in individuals with Pendred syndrome is an enlarged thyroid gland (goitre). This usually becomes noticeable during late childhood or adolescence, although not everyone with Pendred syndrome will develop one. While the goitre might be a cosmetic concern, it is often associated with normal or near-normal thyroid function.
Video: Genetics 101
Affected organs
Pendred syndrome primarily affects the inner ear. Specifically, it impacts the cochlea, which is responsible for hearing, and the vestibular system, which helps with balance. Malformations of these structures, such as an enlarged vestibular aqueduct (EVA), are characteristic features often seen on imaging studies of the inner ear in individuals with the condition [PMID:28795583].
The thyroid gland is the other main organ that can be affected. The thyroid is a butterfly-shaped gland located in the neck that produces hormones essential for metabolism. In Pendred syndrome, the thyroid may enlarge, forming a goitre, but typically maintains its normal function. Rarely, mild hypothyroidism (underactive thyroid) can occur.
Risks & severity
The severity of hearing loss in Pendred syndrome is variable, ranging from moderate to profound. It is usually progressive, meaning it can worsen over time. The age of onset for hearing loss is typically congenital or in early childhood. The risk of developing a goitre is also variable; not all individuals with Pendred syndrome will develop one, and if it does occur, it usually appears later in childhood or adolescence. The goitre is generally benign, though its size can vary.
While the primary impact of Pendred syndrome is on hearing and potentially the thyroid, it does not typically affect life expectancy or cognitive development. Early diagnosis and intervention for hearing loss, such as hearing aids or cochlear implants, are crucial for supporting speech and language development and overall quality of life. Regular monitoring of thyroid function is also recommended for those who develop a goitre.
Genetic causes
Pendred syndrome is caused by pathogenic variants in the SLC26A4 gene. This gene provides instructions for making a protein called pendrin. Pendrin is a transporter protein found in various tissues, including the inner ear and the thyroid gland [PMID:33678077].
In the inner ear, pendrin plays a critical role in maintaining the correct balance of ions, particularly chloride, iodide, and bicarbonate, within the fluid-filled spaces. This ion balance is essential for the proper development and function of hair cells, which detect sound vibrations and send signals to the brain. Pathogenic variants in SLC26A4 disrupt the normal function of pendrin, leading to abnormal ion transport, which in turn impairs the development and function of the inner ear, resulting in hearing loss and inner ear malformations. In the thyroid gland, pendrin is involved in transporting iodide, a key component of thyroid hormones. When pendrin function is disrupted, the thyroid may compensate by enlarging, leading to a goitre.
- SLC26A4 solute carrier family 26 member 4The SLC26A4 gene provides instructions for the pendrin protein, crucial for ion transport in the inner ear and thyroid gland, and is associated with conditions like Pendred syndrome.
Inheritance pattern
Pendred syndrome is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the altered SLC26A4 gene - one from each parent - to develop the condition. People who have only one altered copy of the gene are known as carriers. Carriers typically do not show any signs or symptoms of Pendred syndrome.
If both parents are carriers of a pathogenic variant in SLC26A4, there is a 25% (1 in 4) chance with each pregnancy that their child will inherit two altered copies and be affected by Pendred syndrome. There is a 50% (2 in 4) chance that their child will be a carrier, and a 25% (1 in 4) chance that their child will inherit two working copies of the gene and will not be affected or be a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Pendred syndrome typically begins with the observation of early-onset hearing loss. Further investigations often include audiological assessments to characterise the hearing impairment and imaging studies, such as an MRI of the inner ear, to look for characteristic structural abnormalities like an enlarged vestibular aqueduct (EVA) [PMID:28795583].
Confirmation of Pendred syndrome is made through genetic testing, which identifies pathogenic variants in the SLC26A4 gene. In the UK, genetic testing for hearing loss is available through the NHS Genomic Medicine Service (GMS). Referral for genetic testing is usually made by an audiologist, ear, nose, and throat (ENT) specialist, or clinical geneticist. Relevant NHS Genomic Test Directories for inherited hearing loss include tests under the R-code R115.
Management & lifestyle
Management for individuals with Pendred syndrome focuses on addressing the primary symptoms and monitoring for potential complications. For hearing loss, early intervention is key. This may involve the use of hearing aids, and for those with profound hearing loss, cochlear implants can be a very effective option to improve hearing and support speech development [PMID:28795583]. Regular audiology assessments are important to monitor hearing stability.
If a goitre develops, it is typically monitored, and thyroid function tests are usually carried out to check for any hormone imbalances. Most individuals maintain normal thyroid function, but in rare cases where hypothyroidism occurs, it can be managed with thyroid hormone replacement therapy. Genetic counselling is also an important part of management, offering information about the condition, its inheritance pattern, and support for families.
UK care pathway
In the UK, individuals suspected of having Pendred syndrome would typically enter the NHS Genomic Medicine Service (GMS) pathway. This often begins with a referral from a specialist, such as an audiologist or ENT consultant, to a clinical genetics service. Genetic counsellors within these services provide essential support, explaining genetic test results and their implications for the individual and their family. Testing for inherited hearing loss, including Pendred syndrome, is available via the NHS Genomic Test Directory, under specific R-codes like R115 for sensorineural hearing impairment.
Frequently asked questions
What is the main difference between Pendred syndrome and other types of hearing loss?
Pendred syndrome is distinct because it combines sensorineural hearing loss with the potential for an enlarged thyroid gland (goitre) and characteristic inner ear malformations. Many other types of hearing loss do not have these associated features.
Will everyone with Pendred syndrome develop a goitre?
No, not everyone with Pendred syndrome will develop a goitre. While it is a recognised feature, its occurrence is variable, and it typically appears later in childhood or adolescence if it does develop.
Can Pendred syndrome be treated?
While there isn't a cure for the genetic cause of Pendred syndrome, the symptoms can be effectively managed. Hearing loss can be addressed with hearing aids or cochlear implants, and thyroid issues, if they arise, can be managed with medication.
How is Pendred syndrome diagnosed in the UK?
Diagnosis in the UK involves clinical assessment of hearing, imaging of the inner ear (like an MRI), and confirmation through genetic testing via the NHS Genomic Medicine Service. Referral usually comes from an audiologist or ENT specialist.
Does Pendred syndrome affect learning or development?
Pendred syndrome does not directly affect learning abilities or cognitive development. However, early and effective management of hearing loss is crucial to support speech and language development and prevent potential educational challenges.