Pendred Syndrome and DFNB4

Gene: SLC26A4

Protein: pendrin

Clinical Characteristics

Pendred Syndrome

  • Sensorineural hearing loss:
    • Usually bilateral
    • Usually severe to profound
    • Onset typically at birth or in early childhood
  • Temporal bone abnormalities:
    • Enlarged vestibular aqueduct
    • Cochlear hypoplasia may or may not be present
  • Significant variability within and between families:
    • Enlarged vestibular aqueduct is typical
    • Cochlear hypoplasia may or may not be present
  • Euthyroid goiter, onset in early adulthood


  • Nonsyndromic sensorineural hearing loss
  • Temporal bone abnormalities

Absence of thyroid defects

Inheritance pattern: Autosomal recessive

What Can Be Learned From This Test

Molecular testing of the SLC26A4 gene should be considered for individuals with hearing loss and enlarged vestibular aqueduct (EVA). Testing is performed by sequencing all exons and the surrounding intronic regions of the SLC26A4 gene. This assay will detect point mutations, small deletions and small insertions. It will not detect a partial or whole gene deletion or duplication.

SLC26A4 mutations are identified in 80%-90% of familial cases of Pendred syndrome, and in about 30% of cases with no family history. Mutations have been identified throughout the SLC26A4 gene and include point mutations, small insertions or deletions, and splice site mutations. Deletions of single and multiple exons have also been reported.

The detection of two pathogenic mutations in SLC26A4 is consistent with a diagnosis of Pendred syndrome or DFNB4. However, single heterozygous mutations have been identified in SLC26A4 in 20-30% of individuals who meet criteria for Pendred syndrome or DFNB4. It is hypothesized that a second unidentified mutation is present in SLC26A4 or in another gene. There is some evidence to suggest that individuals with one identified mutation in SLC26A4 are less likely to develop thyroid manifestations than individuals with two identified mutations.

Sample Requirements

Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).

Turnaround time: 10-14 business days

CPT Codes and Cost

Full Gene Sequencing

  • Code: 81406
  • Cost: $1,550

Known Variant Testing

  • Code: 81479
  • Cost: $225

Additional Information