Pendred syndrome.

Pendred Syndrome, first described in 1896, is phenotypically characterized as the coexistence of sensorineural deafness and enlarged goiter with elevated iodine discharge after perchlorate administration. In 1996 the syndrome was mapped to chromosome 7 and the following year, the responsible gene was cloned and mutations were identified. The gene, pds, codes for a 780 amino acid protein, pendrin, which functions as an ion transporter. Located on the apical membrane of thyrocytes, it appears to be responsible for the transport of iodide out of the cell into the colloid where iodination of thyroglobulin occurs, catalyzed by the enzyme thyroid peroxidase. In the absence of the transporter, apical iodide transport is defective and thus organification of iodide is defective, the hallmark of Pendred Syndrome. However, organification is only partially deficient, even in the complete absence of pendrin, suggesting that other, as yet undefined, mechanisms exist that can partially compensate for lack of the protein. The pathophysiology of the hearing loss associated with Pendred syndrome is less well understood. Animal studies suggest that abnormal transporter function may cause abnormal endolymphatic pressure or composition and this results in secondary degeneration of sensory cells and in structural changes of the inner ear. This mechanism, although yet to be proven, suggests the intriguing possibility that early diagnosis and intervention could perhaps prevent at least some of the hearing loss.