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Pendred Syndrome, Genetic Testing

Pendred syndrome is a genetic disorder characterized by congenital sensorineural hearing loss and an enlarged vestibular aqueduct (EVA), which is a dilation of the inner ear's vestibular aqueduct. Pendred syndrome is a form of non-syndromic hearing loss, meaning that hearing loss is the primary feature without additional associated syndromic features.

Pendred syndrome genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

Critical features of Pendred syndrome include:

  • Congenital Sensorineural Hearing Loss: Hearing loss is present from birth and is typically bilateral (affecting both ears). The severity of hearing loss can vary, ranging from mild to profound.
  • Enlarged Vestibular Aqueduct (EVA): EVA is a radiological finding associated with Pendred syndrome. The vestibular aqueduct is a bony canal that connects the inner ear to the skull's inner surface. In Pendred syndrome, this canal is enlarged, which can contribute to hearing loss.
  • Goiter (Thyroid Enlargement): Many individuals with Pendred syndrome may develop a goiter, an enlarged thyroid gland. However, the goiter may not be present in all individuals or may develop later in life.
  • Iodine Organification Defect: Some individuals with Pendred syndrome may have an iodine organification defect, impairing thyroid hormone synthesis.
  • Autosomal Recessive Inheritance: Pendred syndrome is typically inherited in an autosomal recessive manner. Individuals with Pendred syndrome inherit mutations in the SLC26A4 gene from both parents.
  • Variable Expression: The severity of features and the age of onset can vary among affected individuals, even within the same family.

Pendred syndrome is caused by mutations in the SLC26A4 gene, which encodes a protein known as pendrin. Pendrin is involved in the transport of ions, including iodine, in various tissues, including the inner ear and the thyroid gland.

Diagnosis of Pendred syndrome involves clinical evaluation, audiometric testing, imaging studies (such as computed tomography or magnetic resonance imaging to assess the vestibular aqueduct), and genetic testing to identify mutations in the SLC26A4 gene.

Management of Pendred syndrome may include hearing aids or cochlear implants to address the hearing loss. Thyroid function should be monitored, and treatment with thyroid hormone replacement therapy may be initiated if necessary.

Genetic counseling is essential for families affected by Pendred syndrome to understand the inheritance pattern, assess the risk of having affected children, and discuss available reproductive options. Early diagnosis and intervention can help optimize outcomes for individuals with Pendred syndrome, particularly in addressing hearing loss.

More Information

Mutations in the SLC26A4 gene are among the most common causes of hereditary hearing loss. They are responsible for both Pendred syndrome and the autosomal recessive-4 (called DFNB4) non-syndromic deafness that also causes enlargement of the vestibular aqueduct of the ear.

This test includes the predominant variant in Caucasian patients called c.1001+1G>A and other variants of the SLC26A4 gene that are frequent in this population such as c.412G>T (p.V138F), c.1246A>C (p.T416P), c.707T>C (p.L236P) and c.626G>T (p.G209V).

The c.412G>T variant (p.V138F) has been linked in multiple studies to Pendred syndrome. This variant has been found to affect the subcellular localization of pendrin, causing it to be retained in the endoplasmic reticulum and reach its destination, where it exerts its function as an ion transport channel correctly in the cell membrane. c.412G>T is most prevalent in Germany and the Czech Republic. Other variants resulting in the retention of pendrin in the reticulum have also been described, such as c.1151A>G (p.E384G).

The c.2168A>G (p.H723R) and c.919-2A>G mutations (also discussed here) are the two most frequent variants in East Asian patients. Other variants, predominant in China, are c.1226G>A (p.R409H), c.1229C>T (p.T410M), and c.2027T>A (p.L676Q).

The variant c.1334T>G (p.L445W) has also been reported in association with Pendred syndrome and is especially frequent in Iran.

Pendred syndrome genetic testing analyzes the 31 most frequent pathogenic mutations of the SLC26A4 gene.

The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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