Pendred Syndrome is a rare genetic disorder affecting hearing and the thyroid gland. It is considered one of the most common forms of syndromic deafness, where hearing loss occurs alongside other symptoms. The condition typically causes sensorineural hearing loss, often present at birth or developing early in childhood, and may lead to the development of an enlarged thyroid gland, known as a goiter. Early recognition is important for managing symptoms and planning long-term care.
Defining Features and Genetic Origin
The defining features of this syndrome are bilateral sensorineural hearing loss and the potential for a goiter, an enlargement of the thyroid gland. The hearing loss is often severe to profound and may be progressive. The goiter typically develops later, usually appearing during late childhood or early adulthood, and often does not cause the thyroid to malfunction.
The cause of Pendred Syndrome is traced to mutations in the SLC26A4 gene. This gene provides instructions for making pendrin, a protein that acts as an anion transporter. Pendrin is responsible for moving negatively charged ions, such as chloride, iodide, and bicarbonate, across cell membranes in the inner ear and the thyroid gland.
Pendred Syndrome is inherited in an autosomal recessive pattern. This means an individual must inherit a mutated copy of the SLC26A4 gene from both parents to develop the condition. If both parents carry one copy of the mutated gene, they are typically unaffected but have a one in four chance of passing the syndrome to their child. The mutations impair the activity of the pendrin protein, disrupting ion transport in affected organs.
Impact on Hearing and Inner Ear Structure
The primary symptom is hearing loss, which results from structural abnormalities and fluid imbalances within the inner ear. Pendrin is expressed in the cochlea and vestibule, where it regulates the composition of the endolymphatic fluid. This fluid is necessary for the proper functioning of the hair cells that detect sound.
When the pendrin protein is defective, it cannot properly transport ions, disrupting the delicate fluid balance in the inner ear. This imbalance is thought to cause the loss of sensory cells and can affect the development of inner ear structures. The hearing loss is often present from birth and can fluctuate or progress, sometimes worsening after minor head trauma.
A common characteristic seen on imaging is an Enlarged Vestibular Aqueduct (EVA), a bony canal that is wider than normal. The vestibular aqueduct is dilated in most patients with the syndrome. A more complex malformation, known as Mondini dysplasia, may also be present, involving a cochlea with fewer than the normal two-and-a-half turns.
The combination of EVA and Mondini dysplasia is highly suggestive of Pendred Syndrome, as these malformations are the physical manifestation of the defective pendrin protein during development. The inner ear problems can also lead to vestibular dysfunction, although this is not always noticeable in daily life.
Establishing a Diagnosis
Diagnosing Pendred Syndrome involves a combination of clinical evaluation, specialized hearing tests, and imaging studies to look for characteristic findings. Audiological testing, such as Auditory Brainstem Response (ABR) and pure tone audiometry, confirms the presence and severity of the sensorineural hearing loss.
Imaging of the temporal bone is performed using computed tomography (CT) or magnetic resonance imaging (MRI) scans. These scans identify the inner ear malformations associated with the syndrome, particularly the presence of an Enlarged Vestibular Aqueduct (EVA). EVA is considered a hallmark finding that supports the clinical suspicion.
The definitive diagnosis relies on molecular genetic testing, which analyzes a blood sample to confirm biallelic mutations in the SLC26A4 gene. Identifying the specific genetic changes confirms the condition and helps distinguish it from other forms of hearing loss. A perchlorate discharge test can also assess the thyroid’s ability to process iodine, further supporting the diagnosis.
Management and Long-Term Care
Management of Pendred Syndrome focuses on addressing the two main symptoms: hearing loss and potential thyroid dysfunction. Since there is no cure for the underlying genetic defect, intervention is supportive and aims to optimize communication and health outcomes. Early intervention for hearing loss is beneficial for language development.
For hearing loss, treatment options include hearing aids or a cochlear implant for individuals with severe to profound hearing loss. A cochlear implant is an electronic device surgically placed in the inner ear that stimulates the auditory nerve. Due to the inner ear malformations, the surgical procedure for a cochlear implant may be more complex.
Long-term care requires regular monitoring of thyroid function, even if hormone levels are initially normal. Patients should have periodic checks with an endocrinologist to detect the development of a goiter or hypothyroidism. If hypothyroidism develops, it is managed with hormone replacement therapy.
Regular follow-up visits with specialists, including audiologists, otolaryngologists, and endocrinologists, are important to track the progression of hearing loss and manage changes in thyroid health. Genetic counseling is also offered to families to explain the inheritance pattern and risks for future children.