Pendred syndrome is a genetic clinical syndrome classically characterized by the combination of congenital bilateral sensorineural deafness and the development of a goiter.
The disorder is caused by biallelic loss-of-function mutations in the SLC26A4 gene.
This gene encodes for the anion exchanger protein known as pendrin, which acts as a chloride-iodide transport protein.
Pathophysiology
In normal thyroid physiology, pendrin facilitates the essential transport of iodide across the apical membrane of the thyroid follicular cell into the colloid.
Once in the colloid, the iodide undergoes organification and is incorporated into the tyrosine residues on thyroglobulin.
Mutations in the SLC26A4 gene impair this iodide efflux, resulting in a partial iodide organification defect.
Pendrin is also heavily expressed in the inner ear, where it is vital for normal anion transport, thereby explaining the profound sensorineural deafness associated with the syndrome.
Although pendrin also functions as a chloride/bicarbonate exchanger in the kidney, affected patients characteristically do not manifest any renal abnormalities.
Clinical Features and Diagnosis
The hallmark clinical features are congenital sensorineural hearing loss and the presence of a goiter.
The thyroid phenotype is generally mild, and the development of the goiter along with mild hypothyroidism exhibits variable onset even within the same family.
The severity of the thyroid dysfunction in these patients is highly dependent on their dietary nutritional iodine intake.
Diagnostically, patients with SLC26A4 variants and impaired iodide organification will characteristically demonstrate a positive perchlorate discharge test.
