Pendred syndrome

Other Names: PDS; Deafness with goiter; Goiter-deafness syndrome; Autosomal recessive sensorineural hearing impairment and goiter

Pendred syndrome is a condition usually characterized by sensorineural hearing loss in both ears (bilateral) and euthyroid goiter (enlargement of the thyroid gland with normal thyroid gland function). A goiter is an enlargement of the thyroid gland, which is a butterfly-shaped organ at the base of the neck that produces hormones. If a goiter develops in a person with Pendred syndrome, it usually forms between late childhood and early adulthood. In most cases, this enlargement does not cause the thyroid to malfunction. In most people with Pendred syndrome, severe to profound hearing loss caused by changes in the inner ear (sensorineural hearing loss) is evident at birth. Less commonly, hearing loss does not develop until later in infancy or early childhood.

Epidemiology

The prevalence of Pendred syndrome is unknown. However, researchers estimate that it accounts for 7 to 8 percent of all hearing loss that is present from birth (congenital hearing loss).

Cause

Mutations in the SLC26A4 gene cause about half of all cases of Pendred syndrome. The SLC26A4 gene provides instructions for making a protein called pendrin. This protein transports negatively charged particles (ions), including chloride, iodide, and bicarbonate, into and out of cells. Although the function of pendrin is not fully understood, this protein is important for maintaining the proper levels of ions in the thyroid and the inner ear. Mutations in the SLC26A4 gene alter the structure or function of pendrin, which disrupts ion transport. An imbalance of particular ions disrupts the development and function of the thyroid gland and structures in the inner ear, which leads to the characteristic features of Pendred syndrome.

In people with Pendred syndrome who do not have mutations in the SLC26A4 gene, the cause of the condition is unknown. Researchers suspect that other genetic and environmental factors may influence the condition.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

Some affected individuals also have problems with balance caused by dysfunction of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation.

An inner ear abnormality called an enlarged vestibular aqueduct (EVA) is a characteristic feature of Pendred syndrome. The vestibular aqueduct is a bony canal that connects the inner ear with the inside of the skull. Some affected individuals also have an abnormally shaped cochlea, which is a snail-shaped structure in the inner ear that helps process sound. The combination of an enlarged vestibular aqueduct and an abnormally shaped cochlea is known as Mondini malformation.

Pendred syndrome shares features with other hearing loss and thyroid conditions, and it is unclear whether they are best considered as separate disorders or as a spectrum of related signs and symptoms. These conditions include a form of nonsyndromic hearing loss (hearing loss that does not affect other parts of the body) called DFNB4, and, in a small number of people, a form of congenital hypothyroidism resulting from an abnormally small thyroid gland (thyroid hypoplasia). All of these conditions are caused by mutations in the same gene.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Enlarged vestibular aqueduct
• Hypoplasia of the cochlea
• Sensorineural hearing impairment

30%-79% of people have these symptoms

• Goiter(Enlarged thyroid gland in neck)
• Hypothyroidism(Underactive thyroid)

5%-29% of people have these symptoms

• Ataxia
• Hyperparathyroidism(Elevated blood parathyroid hormone level)
• Intellectual disability(Mental deficiency)
• Nephropathy
• Neurological speech impairment(Speech disorder)
• Respiratory insufficiency(Respiratory impairment)
• Thyroid carcinoma
• Tracheal stenosis(Narrowing of windpipe)
• Vertigo(Dizzy spell)

Diagnosis

In at least 50% of probands with Pendred syndrome and/or NSEVA, the molecular diagnosis is established by identification of biallelic pathogenic variants in SLC26A4 or double heterozygosity for one pathogenic variant in SLC26A4 and one pathogenic variant in either FOXI1 or KCNJ10.

The clinical diagnosis of Pendred syndrome is established in a proband with SNHL, characteristic temporal bone abnormalities identified on thin-cut CT, and euthyroid goiter. In comparison, the clinical diagnosis of nonsyndromic enlarged vestibular aqueduct (NSEVA) is established in a proband with SNHL and the temporal bone finding of enlargement of the vestibular aqueducts.

It is important to note that in PDS, the temporal bone abnormality can include both EVA and cochlear hypoplasia, an anomaly in which the cochlea has only 1.5 turns instead of the expected 2.75 turns. In NSEVA, the temporal bone abnormality is restricted to EVA, defined as a vestibular aqueduct that exceeds 1.5 mm in width at its midpoint. This distinction is relevant because thyroid enlargement is variably present, depending on methods used to assess thyroid size and nutritional iodine intake. Some studies have suggested that a goiter is present in only 50% of affected individuals.

Treatment

Hearing habituation, hearing aids, and educational programs designed for the hearing impaired; consideration of cochlear implantation in individuals with severe-to-profound deafness; standard treatment of abnormal thyroid function.

Surveillance: Repeat audiometry every three to six months initially if hearing loss is progressive, then semiannually or annually. Baseline ultrasound examination of the thyroid with periodic physical examination and/or ultrasonography to monitor volumetric changes; thyroid function tests every two to three years.

Agents/circumstances to avoid: Some evidence suggests that dramatic increases in intracranial pressure can be associated with a sudden drop in hearing. For this reason, advisability of weightlifting and/or contact sports should be discussed with a physician/health care provider prior to participation.

NIH genetic and rare disease info

• NIH info on Pendred syndrome

Pendred syndrome is a rare disease.

Pendred syndrome Resources
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