Pendred syndrome is a genetic disorder leading to congenital bilateral (both sides) sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism (decreased 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 after Vaughan Pendred (1869–1946), the British doctor who first described the condition in an Irish family living in Durham in 1896.[2][3] It accounts for 7.5% to 15% of all cases of congenital deafness.[4]
The normal cochlea has 2 & a half turns, but, in Pendred Syndrome, there is abnormal partitioning (the central bony core is reduced in size and complexity)and a reduced number of turns leading to a Mondini cochlea which has a basal turn and a dilated apical turn (1 & a half turns). There is also a dilated endolymphatic duct and sac with a widened vestibular aqueduct
The hearing loss of Pendred syndrome is often, although not always, present from birth, and language acquisition may be a significant problem if deafness is severe in childhood. The hearing loss typically worsens over the years, and progression can be step-wise and related to minor head trauma. In some cases, language development worsens after head injury, demonstrating that the inner ear is sensitive to trauma in Pendred syndrome; this is as a consequence of the widened vestibular aqueducts usual in this syndrome.[4] Vestibular function varies in Pendred syndrome and vertigo can be a feature of minor head trauma. A goitre is present in 75% of all cases.[4]
Geneticsedit
Pendred syndrome has an autosomal recessive pattern of inheritance.
Pendred syndrome is inherited 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 syndrome has a 25% chance of also having the condition if the parents are unaffected carriers.[5]
It has been linked to mutations in the PDSgene, which codes for the pendrin protein (solute carrier family 26, member 4, SLC26A4). The gene is located on the long arm of chromosome 7 (7q31).[6][7] 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.[8]
Pathophysiologyedit
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 syndrome is not known to lead to kidney problems.[9] It functions as an iodide/chloride transporter.[10] In the thyroid, this leads to reduced organification of iodine (i.e. its incorporation into thyroid hormone).[6]
Diagnosisedit
People with Pendred syndrome present with a hearing loss either at birth or during childhood. The hearing loss is commonly progressive. In early stages it is usually a mixed hearing loss (both conductive and sensorineural hearing loss) because of a third window effect due to the inner ear malformation (widened vestibular aqueducts). A thyroid goitre may be present in the first decade and is usual towards the end of the second decade. MRI scanning of the inner ear usually shows widened or large vestibular aqueducts with enlarged endolymphatic sacs and may show abnormalities of the cochleae that are known as Mondini dysplasia.[4]Genetic testing to identify the pendrin gene usually establishes the diagnosis. If the condition is suspected, a "perchlorate discharge test" is sometimes performed. This test is highly sensitive, but may also be abnormal in other thyroid conditions.[4] 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.[11]
Treatmentedit
No specific treatment exists for Pendred syndrome. If thyroid hormone levels are decreased, thyroid hormone supplements may be required. Patients are advised to take precautions against head injury.[11]
Referencesedit
^RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Pendred syndrome". www.orpha.net. Retrieved 29 September 2019.{{cite web}}: CS1 maint: numeric names: authors list (link)
^Pendred V (1896). "Deaf-mutism and goitre". Lancet. 2 (3808): 532. doi:10.1016/S0140-6736(01)74403-0.
^ abcdeReardon W, Coffey R, Phelps PD, et al. (July 1997). "Pendred syndrome--100 years of underascertainment?". QJM. 90 (7): 443–7. doi:10.1093/qjmed/90.7.443. PMID 9302427.
^Wémeau JL, Kopp P (March 2017). "Pendred syndrome". Best Practice & Research. Clinical Endocrinology & Metabolism. 31 (2): 213–224. doi:10.1016/j.beem.2017.04.011. PMID 28648509.
^ abSheffield VC, Kraiem Z, Beck JC, et al. (April 1996). "Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification". Nat. Genet. 12 (4): 424–6. doi:10.1038/ng0496-424. PMID 8630498. S2CID 25888014.
^Coyle B, Coffey R, Armour JA, Gausden E, Hochberg Z, Grossman A, et al. (April 1996). "Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4". Nature Genetics. 12 (4): 421–3. doi:10.1038/ng0496-421. PMID 8630497. S2CID 7166946.
^Azaiez H, Yang T, Prasad S, Sorensen JL, Nishimura CJ, Kimberling WJ, Smith RJ (December 2007). "Genotype-phenotype correlations for SLC26A4-related deafness". Human Genetics. 122 (5): 451–7. doi:10.1007/s00439-007-0415-2. PMC10519375. PMID 17690912. S2CID 19451595.
^Royaux IE, Wall SM, Karniski LP, et al. (March 2001). "Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion". Proc. Natl. Acad. Sci. U.S.A. 98 (7): 4221–6. Bibcode:2001PNAS...98.4221R. doi:10.1073/pnas.071516798. PMC31206. PMID 11274445.
^Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP (April 1999). "The Pendred syndrome gene encodes a chloride-iodide transport protein". Nature Genetics. 21 (4): 440–3. doi:10.1038/7783. PMID 10192399. S2CID 23717390.
^ abNational Institute on Deafness and Other Communication Disorders (October 2006). . Archived from the original on 2008-05-09. Retrieved 2008-05-05.
External linksedit
GeneReviews/NCBI/NIH/UW entry on Pendred Syndrome/DFNB4
NCBI Genes and Diseases
December 15, 2023
pendred, syndrome, genetic, disorder, leading, congenital, bilateral, both, sides, sensorineural, hearing, loss, goitre, with, euthyroid, mild, hypothyroidism, decreased, thyroid, gland, function, there, specific, treatment, other, than, supportive, measures, . Pendred syndrome is a genetic disorder leading to congenital bilateral both sides sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism decreased 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 after Vaughan Pendred 1869 1946 the British doctor who first described the condition in an Irish family living in Durham in 1896 2 3 It accounts for 7 5 to 15 of all cases of congenital deafness 4 Pendred syndromeOther namesGoiter deafness syndrome 1 The normal cochlea has 2 amp a half turns but in Pendred Syndrome there is abnormal partitioning the central bony core is reduced in size and complexity and a reduced number of turns leading to a Mondini cochlea which has a basal turn and a dilated apical turn 1 amp a half turns There is also a dilated endolymphatic duct and sac with a widened vestibular aqueductSpecialtyEndocrinology Named afterVaughan Pendred Contents 1 Signs and symptoms 2 Genetics 3 Pathophysiology 4 Diagnosis 5 Treatment 6 References 7 External linksSigns and symptoms editThe hearing loss of Pendred syndrome is often although not always present from birth and language acquisition may be a significant problem if deafness is severe in childhood The hearing loss typically worsens over the years and progression can be step wise and related to minor head trauma In some cases language development worsens after head injury demonstrating that the inner ear is sensitive to trauma in Pendred syndrome this is as a consequence of the widened vestibular aqueducts usual in this syndrome 4 Vestibular function varies in Pendred syndrome and vertigo can be a feature of minor head trauma A goitre is present in 75 of all cases 4 Genetics edit nbsp Pendred syndrome has an autosomal recessive pattern of inheritance Pendred syndrome is inherited 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 syndrome has a 25 chance of also having the condition if the parents are unaffected carriers 5 It has been linked to mutations 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 7q31 6 7 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 8 Pathophysiology editSLC26A4 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 syndrome is not known to lead to kidney problems 9 It functions as an iodide chloride transporter 10 In the thyroid this leads to reduced organification of iodine i e its incorporation into thyroid hormone 6 Diagnosis editPeople with Pendred syndrome present with a hearing loss either at birth or during childhood The hearing loss is commonly progressive In early stages it is usually a mixed hearing loss both conductive and sensorineural hearing loss because of a third window effect due to the inner ear malformation widened vestibular aqueducts A thyroid goitre may be present in the first decade and is usual towards the end of the second decade MRI scanning of the inner ear usually shows widened or large vestibular aqueducts with enlarged endolymphatic sacs and may show abnormalities of the cochleae that are known as Mondini dysplasia 4 Genetic testing to identify the pendrin gene usually establishes the diagnosis If the condition is suspected a perchlorate discharge test is sometimes performed This test is highly sensitive but may also be abnormal in other thyroid conditions 4 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 11 Treatment editNo specific treatment exists for Pendred syndrome If thyroid hormone levels are decreased thyroid hormone supplements may be required Patients are advised to take precautions against head injury 11 References edit RESERVED INSERM US14 ALL RIGHTS Orphanet Pendred syndrome www orpha net Retrieved 29 September 2019 a href Template Cite web html title Template Cite web cite web a CS1 maint numeric names authors list link Pendred V 1896 Deaf mutism and goitre Lancet 2 3808 532 doi 10 1016 S0140 6736 01 74403 0 Pearce JM 2007 Pendred s syndrome Eur Neurol 58 3 189 90 doi 10 1159 000104724 PMID 17622729 a b c d e Reardon W Coffey R Phelps PD et al July 1997 Pendred syndrome 100 years of underascertainment QJM 90 7 443 7 doi 10 1093 qjmed 90 7 443 PMID 9302427 Wemeau JL Kopp P March 2017 Pendred syndrome Best Practice amp Research Clinical Endocrinology amp Metabolism 31 2 213 224 doi 10 1016 j beem 2017 04 011 PMID 28648509 a b Sheffield VC Kraiem Z Beck JC et al April 1996 Pendred syndrome maps to chromosome 7q21 34 and is caused by an intrinsic defect in thyroid iodine organification Nat Genet 12 4 424 6 doi 10 1038 ng0496 424 PMID 8630498 S2CID 25888014 Coyle B Coffey R Armour JA Gausden E Hochberg Z Grossman A et al April 1996 Pendred syndrome goitre and sensorineural hearing loss maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4 Nature Genetics 12 4 421 3 doi 10 1038 ng0496 421 PMID 8630497 S2CID 7166946 Azaiez H Yang T Prasad S Sorensen JL Nishimura CJ Kimberling WJ Smith RJ December 2007 Genotype phenotype correlations for SLC26A4 related deafness Human Genetics 122 5 451 7 doi 10 1007 s00439 007 0415 2 PMC 10519375 PMID 17690912 S2CID 19451595 Royaux IE Wall SM Karniski LP et al March 2001 Pendrin encoded by the Pendred syndrome gene resides in the apical region of renal intercalated cells and mediates bicarbonate secretion Proc Natl Acad Sci U S A 98 7 4221 6 Bibcode 2001PNAS 98 4221R doi 10 1073 pnas 071516798 PMC 31206 PMID 11274445 Scott DA Wang R Kreman TM Sheffield VC Karniski LP April 1999 The Pendred syndrome gene encodes a chloride iodide transport protein Nature Genetics 21 4 440 3 doi 10 1038 7783 PMID 10192399 S2CID 23717390 a b National Institute on Deafness and Other Communication Disorders October 2006 Pendred Syndrome Archived from the original on 2008 05 09 Retrieved 2008 05 05 External links editGeneReviews NCBI NIH UW entry on Pendred Syndrome DFNB4 NCBI Genes and Diseases Retrieved from https en wikipedia org w index php title Pendred syndrome amp oldid 1184011904, wikipedia, wiki, book, books, library,
