Pendred syndrome

Pendred syndrome (also known as Pendred's syndrome or goiter-deafness syndrome) is an autosomal recessive disorder characterized by the combination of sensorineural hearing loss and thyroid dysfunction. It is caused by biallelic pathogenic variants in the SLC26A4 gene (formerly known as PDS), which encodes pendrin, an anion transporter expressed in the inner ear, thyroid gland, and kidney. Pendred syndrome is considered one of the most common forms of syndromic hearing loss, potentially accounting for up to 10% of hereditary deafness cases. The hearing loss in Pendred syndrome is typically bilateral, sensorineural, and can range from moderate to profound. It is often congenital or develops in early childhood and may be progressive or fluctuating. A hallmark inner ear malformation is an enlarged vestibular aqueduct (EVA), which is present in most affected individuals and can be detected on temporal bone imaging. Some patients also have a Mondini malformation (incomplete cochlear partition). Vestibular dysfunction, including episodes of vertigo, may also occur. The thyroid abnormality manifests as a euthyroid or hypothyroid goiter, typically developing in late childhood or adolescence. The goiter results from a defect in iodide organification in the thyroid, which can be demonstrated by a positive perchlorate discharge test. There is currently no cure for Pendred syndrome. Management is multidisciplinary and focuses on addressing the individual manifestations. Hearing loss is managed with hearing aids or cochlear implantation when appropriate. Thyroid function should be monitored regularly, and thyroid hormone replacement therapy (levothyroxine) is indicated if hypothyroidism develops. Patients are advised to avoid head trauma and activities that could cause sudden pressure changes, as these may worsen hearing loss in the setting of an enlarged vestibular aqueduct. Genetic counseling is recommended for affected families.

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