MED-NERD

Pendred Syndrome

Introduction:

Also known as:
"Pendred syndrome or Goiter-deafness syndrome; autosomal recessive sensorineural hearing impairment and goiter; Deafness with goiter"

Pendred syndrome is an autosomal recessive disorder characterized by a combination of profound to severe sensorineural hearing loss, thyroid goiter with or without hypothyroidism (A partial defect in iodide organification). The syndrome is caused by mutation in the PDS/SLC26A4 gene (OMIM 605646) on chromosome 7 that results in defected pendrin protein which is an ion transporter and a multifunctional anion exchanger protein that is mainly expressed in the thyroid, kidney, and the inner ear. The gene is important to maintain the composition of endolymph and to keep the endocochlear potential through the chloride/bicarbonate exchanger. 

Hearing loss is often sudden and eventually may result in deafness. Hearing loss is usually bilateral but one ear may be affected more than the other.

Pendred syndrome was first described in 1896 by Dr. Vaughan Pendred in an article in “The Lancet” showing the association between deaf-mutism and thyroid goiter. In 1996, the genetic mutation in Pendred syndrome was localized to SLC26A4/PDS gene on chromosome 7q21–34. The main presenting symptom is deafness and is often prelingual. The syndrome may be associated with inner ear malformations (such as enlargement of the endolymphatic system) and Mondini malformation.

In Pendred syndrome, there is an enlargement of the endolymphatic system that can be seen on magnetic resonance imaging (MRI) or computed tomography (CT) as an enlarged vestibular aqueduct (EVA).
It may also be associated with incomplete partition type II (Mondini dysplasia) which is a deficient interscalar septum in the distal coils of the cochlea. About 86% of Pendred syndrome cases are associated with abnormalities such as  EVA with or without enlarged endolymphatic sac (EES) and/or Mondini malformation.

The thyroid may be enlarged up to obstruction of the airway but may be normal in size. More than 15% of radioiodide (radioiodide then becomes organified into thyroglobulin for the synthesis of thyroid hormones) is accumulated in thyrocytes in Pendred syndrome indicating impaired iodide organification ( the normal value is less than 10% of radioiodide accumulated in thyrocytes). However, most Pendred syndrome patients have euthyroid state (normal thyroid hormone level) except if associated with dietary iodine deficiency.

In the United states, researchers found that about 50-60% of hearing loss is genetic, and about 40-50% is due yo environmental causes.
About 10% of hereditary hearing loss is caused by Pendred syndrome (Incidence of 7.5 to 10 in 100,000). It is the most common cause of congenital and syndromic hearing loss.





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