SickKids

Paediatric Laboratory Medicine
Paediatric Laboratory Medicine
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Hearing Loss: Pendred Syndrome

Background
Who should be tested?
Testing Methodology
Potential Outcomes & Interpretation of Test Results
Cautions
For More Information

Background

Pendred syndrome is characterized by congenital sensorineural hearing impairment, temporal bone anomalies, and the development of euthyroid goiter in late childhood to early adulthood.

Pendred syndrome is an autosomal recessive disorder caused by a deficiency of the protein pendrin. The gene responsible for Pendred syndrome, SLC26A, has been localized to chromosome 7q31. Three recurrent mutations account for ~50% of the Pendred mutant alleles in Caucasians of northern European descent who have a confirmed diagnosis of Pendred syndrome: p.Leu236Pro (26%), p.Thr416Pro (15%), and c.1001+G>A (14%). The recurrent mutation p.His723Arg accounts for 53% of mutant alleles among Japanese. In addition, a form of non-syndromic deafness (DNFB4) is also caused by mutations in the SLC26A4 gene. Individuals with this form of deafness have sensorineural hearing loss and temporal bone malformations but do not have thyroid abnormalities.

Pendred syndrome is present when a child receives two copies of a defective gene, one from each parent. Any person with one copy of the defective SLC26A4 gene is a Pendred syndrome carrier. Carriers are not affected themselves by Pendred syndrome and will never develop the disease. However, if their partner is also a carrier, there is a one in four chance (25%) that their baby will be born with Pendred syndrome. There is a three in four chance (75%) that their baby will not have Pendred syndrome.

Who should be tested

  • individuals clinically suspected of being affected with Pendred syndrome
  • relatives of probands with identified mutations in the gene for Pendred syndrome

Testing Methodology

Direct Mutation Analysis: All samples are analyzed by direct sequence analysis of the 22 exons of the SLC26A4 gene.

Test Sensitivity: Mutations in the SLC26A4 gene are responsible for ~50% of affected individuals from multiplex families and 20% of individuals from simplex families.

Potential Outcomes & Interpretation of Test Results

Reason for
referral

SLC26A4 Gene Mutations
allele 1 / allele 2

Explanation

carrier testing

none detected / none detected

  • This individual is unlikely to be a carrier of Pendred syndrome.

carrier testing

mutation detected / none detected

  • This individual is a carrier of Pendred syndrome, and may transmit a mutation to offspring.

diagnosis

none detected / none detected

  • This result does not support a diagnosis of of Pendred syndrome.

diagnosis

mutation detected / none detected

  • This result is unable to confirm a diagnosis of Pendred syndrome.

diagnosis

mutation detected / mutation detected

  • This result supports a diagnosis of Pendred syndrome.

Cautions

  • Current molecular testing will not detect all possible mutations causing Pendred syndrome. A negative result does not rule out the possibility that the individual has a rare mutation not included in the assay and is affected with Pendred syndrome.
  • Test results should be interpreted in the context of clinical findings, family history and other laboratory data.
  • This test was developed and its performance characteristics validated by the Molecular Genetics Laboratory at the Hospital for Sick Children. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes.

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