MED-NERD

Pathophysiology of Pendred syndrome

-Thyroid gland >> Pendrin acts as Cl-/I- exchanger on the apical membrane of thyrocyte which is essential to induce efflux of cellular iodide into the follicular lumen. Therefore, defect in this gene leads to dysfunction and defected thyroid organification. However, most Pendred syndrome patients have euthyroid state so the growth and development of children is usually not affected. The risk of goiter is increased in Pendred syndrome. Goiter usually develops in adolescence or early adulthood. Goiter may cause difficulties in breathing and swallowing due to compression effect. 

-Inner Ear >> Pendrin is important to achieve proper function of inner ear, resorption of endolymphatic fluid, and acid-base balance. It is expressed in the inner ear in the cochlea and vestibule. Vestibular system is necessary to maintain balance. Despite the vestibular weakness that may occur in Pendred syndrome, the brain can usually compensate the defect in vestibular system so most children and adults do not have balance problems in Pendred syndrome cases. Delayed walking may be observed in some Pendred syndrome infants.

-Kidney >> Pendrin has important role in bicarbonate secretion to the tubular lumen and chloride reabsorption, regulation of blood pressure, and fluid balance by acting as a chloride/anion exchanger. It is expressed in the cortical collecting ducts at or near the apical membrane of type B and non A non B intercalated cells. Therefore, metabolic alkalosis may occur due to defect in Pendrin protein.

-Bronchial Epithelium >> Pendin acts as a Chloride/bicarbonate exchanger and regulates the airway surface liquid thickness where it is expressed at the apical membrane of bronchial epithelial cells. Moreover, it has a role in the innate defense mechanism of mucosal surfaces by secreting the antioxidant 'SCN' to the lumen. Therefore, a defect in Pendrin protein affects the production of mucus and has a relation to asthma and Chronic Obstructive Pulmonary Diseas (COPD).

Etiology and Epidemiology of Pendred Syndrome

Reference:

(1)Garabet Diramerian L, Ejaz S. Pendred Syndrome. 2022 Jun 27. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.
https://www.ncbi.nlm.nih.gov/books/NBK549839/
(2)Smith RJH, Iwasa Y, Schaefer AM. Pendred Syndrome / Nonsyndromic Enlarged Vestibular Aqueduct. 1998 Sep 28 [updated 2020 Jun 18]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.
https://www.ncbi.nlm.nih.gov/books/NBK1467/
(3)Gettelfinger JD, Dahl JP. Syndromic Hearing Loss: A Brief Review of Common Presentations and Genetics. J Pediatr Genet. 2018 Mar;7(1):1-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809162/
(4)Biggs K, Lovett A, Metcalfe C, Muzaffar J, Monksfield P, Bance M. Outcomes of Cochlear Implantation in Patients with Pendred syndrome: A Systematic Review and Narrative Synthesis. J Int Adv Otol. 2020 Dec;16(3):432-442.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901456/
(5)Pendred Syndrome,NIH national institute on deafness Nd other communication disorders
https://www.nidcd.nih.gov/health/pendred-syndrome