Pendred syndrome
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2008-06-22T18:26:06Z
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DiseasesDB = 9771 |
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OMIM = 274600 |
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'''Pendred syndrome''' or '''Pendred disease''' is a [[genetic disorder]] leading to congenital bilateral (both sides) [[sensorineural hearing loss]] and [[goitre]] with occasional [[hypothyroidism]] (decreased [[thyroid|thyroid gland]] function). There is no specific treatment, other than supportive measures for the hearing loss and [[thyroid hormone]] supplementation in case of hypothyroidism. It is named Dr Vaughan Pendred (1869-1946), the [[England|English]] doctor who first described the condition in an [[Ireland|Irish]] family living in [[Durham]] in 1896.<ref name=Pendred>{{cite journal | author=Pendred V | title=Deaf-mutism and goitre | journal=Lancet | year=1896 |volume=2 | pages=532 | doi=10.1016/S0140-6736(01)74403-0}}</ref><ref name=Pearce>{{cite journal |author=Pearce JM |title=Pendred's syndrome |journal=Eur. Neurol. |volume=58 |issue=3 |pages=189–90 |year=2007 |pmid=17622729 |doi=10.1159/000104724 |url=http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=000104724&Ausgabe=233307&ProduktNr=223840}}</ref> It accounts for 7.5% of all cases of congenital [[deafness]].<ref name=Reardon/>
==Signs and symptoms==
The hearing loss of Pendred's syndrome is present from birth, and language acquisition may be a significant problem if this is severe in childhood. Hearing typically worsens over the years, and many proceed to deafness at a later age. In some cases, language development worsens after [[head injury]], suggesting that the inner ear is sensitive to trauma in Pendred syndrome.<ref name=Reardon>{{cite journal |author=Reardon W, Coffey R, Phelps PD, ''et al'' |title=Pendred syndrome--100 years of underascertainment? |journal=QJM |volume=90 |issue=7 |pages=443–7 |year=1997 |month=July |pmid=9302427 |url=http://qjmed.oxfordjournals.org/cgi/reprint/90/7/443 | format=PDF |doi=10.1093/qjmed/90.7.443}}</ref> A goitre is present in 75% of all cases.<ref name=Reardon/>
== Diagnosis ==
[[Audiology]] (measuring ability to hear sounds of a particular pitch) is always abnormal, but the findings are not particularly specific and an audiogram is not sufficient to diagnose Pendred's syndrome. If the condition is suspected, a "perchlorate discharge test" is therefore sometimes performed. This test is highly [[sensitivity (test)|sensitive]], but may also be abnormal in other thyroid conditions.<ref name=Reardon/> If a goitre is present, [[thyroid function tests]] are performed to identify mild cases of thyroid dysfunction even if they are not yet causing symptoms.<ref name=NIDCD>{{cite web |author=National Institute on Deafness and Other Communication Disorders | url=http://www.nidcd.nih.gov/health/hearing/pendred.asp |title=Pendred Syndrome |date=October 2006 |accessdate=2008-05-05}}</ref>
Some require [[computed tomography|CT scanning]] or [[Magnetic resonance imaging|MRI scanning]] of the middle ear. This is not always abnormal, but may show an abnormality of the inner ear known as [[Mondini dysplasia]].<ref name=Reardon/>
==Genetics==
[[Image:autorecessive.svg|thumb|right|{{PAGENAME}} has an autosomal recessive pattern of inheritance.]]
Pendred syndrome inherits in an [[autosomal recessive]] manner, meaning that one would need to inherit an abnormal gene from each parent to develop the condition. This also means that a sibling of a patient with Pendred's syndrome has a 25% chance of also having the condition.
It has been linked to [[mutation]]s in the ''PDS'' [[gene]], which codes for the ''[[pendrin]]'' protein (solute carrier family 26, member 4, [[SLC26A4]]). The gene is located on the long arm of [[chromosome 7 (human)|chromosome 7]] (7q31).<ref name=Sheffield>{{cite journal |author=Sheffield VC, Kraiem Z, Beck JC, ''et al'' |title=Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification |journal=Nat. Genet. |volume=12 |issue=4 |pages=424–6 |year=1996 |month=April |pmid=8630498 |doi=10.1038/ng0496-424 |url=}}</ref><ref>{{cite journal |author=Coyle B, Coffey R, Armour JA, ''et al'' |title=Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4 |journal=Nat. Genet. |volume=12 |issue=4 |pages=421–3 |year=1996 |month=April |pmid=8630497 |doi=10.1038/ng0496-421}}</ref> Mutations in the same gene also cause [[enlarged vestibular aqueduct syndrome]] (EVA or EVAS), another congenital cause of deafness; specific mutations are more likely to cause EVAS, while others are more linked with Pendred syndrome.<ref>{{cite journal |author=Azaiez H, Yang T, Prasad S, ''et al'' |title=Genotype-phenotype correlations for SLC26A4-related deafness |journal=Hum. Genet. |volume=122 |issue=5 |pages=451–7 |year=2007 |month=December |pmid=17690912 |doi=10.1007/s00439-007-0415-2}}</ref>
==Pathophysiology==
{{expand|date=May 2008}}
SLC26A4 can be found in the [[cochlea]] (part of the inner ear), [[thyroid]] and the [[kidney]]. In the kidney, it participates in the secretion of [[bicarbonate]]. However, Pendred's syndrome is not known to lead to kidney problems.<ref>{{cite journal |author=Royaux IE, Wall SM, Karniski LP, ''et al'' |title=Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=7 |pages=4221–6 |year=2001 |month=March |pmid=11274445 |doi=10.1073/pnas.071516798 |url=http://www.pnas.org/cgi/content/full/98/7/4221}} {{PMC|31206}}</ref> It functions as an iodide/chloride transporter.{{fact|date=May 2008}} In the thyroid, this leads to reduced organification of iodine (i.e. its incorporation into thyroid hormone).<ref name=Sheffield/>
==Treatment==
No specific treatment exists for Pendred syndrome. [[Speech and language pathology|Speech and language support]], and [[cochlear implant]]s, may improve language skills.<ref name=NIDCD/> If thyroid hormone levels are decreased, [[thyroxine]] may be required. Patients are advised to take precautions against head injury.<ref name=NIDCD/>
==References==
{{reflist}}
==External links==
* [http://www.ncbi.nlm.nih.gov/disease/Pendred.html NCBI Genes and Diseases]
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[[Category:Genetic disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Otology]]
[[Category:Syndromes]]
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