Pendred Syndrome / Nonsyndromic Enlarged Vestibular Aqueduct

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: Pendred syndrome / nonsyndromic enlarged vestibular aqueduct (PDS/NSEVA) comprises a phenotypic spectrum of sensorineural hearing loss (SNHL) that is usually congenital and often severe to profound (although mild-to-moderate progressive hearing impairment also occurs), vestibular dysfunction, and temporal bone abnormalities (bilateral enlarged vestibular aqueduct with or without cochlear hypoplasia). PDS also includes development of euthyroid goiter in late childhood to early adulthood whereas NSEVA does not.

Diagnosis/testing: 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.

Management: Treatment of manifestations: 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.

Genetic counseling: PDS/NSEVA is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. When the family-specific pathogenic variants are known, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.

Publication types

  • Review