Pendred syndrome

Pendred syndrome or Pendred disease is a genetic disorder leading to congenital bilateral (both sides) sensorineural hearing loss and goitre with occasional hypothyroidism (decreased thyroid gland function). There is no specific treatment, other than supportive measures for the hearing loss and thyroid hormone supplementation in case of hypothyroidism. It is named Dr Vaughan Pendred (1869-1946), the English doctor who first described the condition in an Irish family living in Durham in 1896. It accounts for 7.5% of all cases of congenital deafness.

Signs and symptoms
The hearing loss of Pendred's syndrome is present from birth, and language acquisition may be a significant problem if this is severe in childhood. Hearing typically worsens over the years, and many proceed to deafness at a later age. In some cases, language development worsens after head injury, suggesting that the inner ear is sensitive to trauma in Pendred syndrome. A goitre is present in 75% of all cases.

Diagnosis
Audiology (measuring ability to hear sounds of a particular pitch) is always abnormal, but the findings are not particularly specific and an audiogram is not sufficient to diagnose Pendred's syndrome. If the condition is suspected, a "perchlorate discharge test" is therefore sometimes performed. This test is highly sensitive, but may also be abnormal in other thyroid conditions. If a goitre is present, thyroid function tests are performed to identify mild cases of thyroid dysfunction even if they are not yet causing symptoms.

Some require CT scanning or MRI scanning of the middle ear. This is not always abnormal, but may show an abnormality of the inner ear known as Mondini dysplasia.

Genetics


Pendred syndrome inherits in an autosomal recessive manner, meaning that one would need to inherit an abnormal gene from each parent to develop the condition. This also means that a sibling of a patient with Pendred's syndrome has a 25% chance of also having the condition.

It has been linked to mutations in the PDS gene, which codes for the pendrin protein (solute carrier family 26, member 4, SLC26A4). The gene is located on the long arm of chromosome 7 (7q31). Mutations in the same gene also cause enlarged vestibular aqueduct syndrome (EVA or EVAS), another congenital cause of deafness; specific mutations are more likely to cause EVAS, while others are more linked with Pendred syndrome.

Pathophysiology
SLC26A4 can be found in the cochlea (part of the inner ear), thyroid and the kidney. In the kidney, it participates in the secretion of bicarbonate. However, Pendred's syndrome is not known to lead to kidney problems. It functions as an iodide/chloride transporter. In the thyroid, this leads to reduced organification of iodine (i.e. its incorporation into thyroid hormone).

Treatment
No specific treatment exists for Pendred syndrome. Speech and language support, and cochlear implants, may improve language skills. If thyroid hormone levels are decreased, thyroxine may be required. Patients are advised to take precautions against head injury.