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Pendred syndrome(PDS)

MedGen UID:
82890
Concept ID:
C0271829
Disease or Syndrome
Synonyms: DEAFNESS WITH GOITER; Goiter-deafness syndrome; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 2B; PDS; Pendred's syndrome; THYROID DYSHORMONOGENESIS 2B; THYROID HORMONOGENESIS, GENETIC DEFECT IN, 2B
SNOMED CT: Pendred's syndrome (70348004); Hypothyroidism with sensorineural deafness (70348004); Thyroid hormone organification defect II B (70348004); Goiter-deafness syndrome (70348004); Genetic defect in thyroid hormonogenesis II B (70348004); GDTH IIB (70348004); Pendred syndrome (70348004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Genes (locations): FOXI1 (5q35.1); KCNJ10 (1q23.2); SLC26A4 (7q22.3)
 
Monarch Initiative: MONDO:0010134
OMIM®: 274600
Orphanet: ORPHA705

Definition

Pendred syndrome / nonsyndromic enlarged vestibular aqueduct (PDS/NSEVA) comprises a phenotypic spectrum of sensorineural hearing loss (SNHL) that is usually congenital and often severe to profound (although mild-to-moderate progressive hearing impairment also occurs), vestibular dysfunction, and temporal bone abnormalities (bilateral enlarged vestibular aqueduct with or without cochlear hypoplasia). PDS also includes development of euthyroid goiter in late childhood to early adulthood whereas NSEVA does not. [from GeneReviews]

Additional descriptions

From OMIM
Pendred syndrome, the most common syndromal form of deafness, is an autosomal recessive disorder associated with developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter) (Everett et al., 1997). For a general phenotypic description and a discussion of genetic heterogeneity of thyroid dyshormonogenesis, see TDH1 (274400).  http://www.omim.org/entry/274600
From MedlinePlus Genetics
Pendred syndrome is a disorder typically associated with hearing loss and a thyroid condition called a goiter. A goiter is an enlargement of the thyroid gland, which is a butterfly-shaped organ at the base of the neck that produces hormones. If a goiter develops in a person with Pendred syndrome, it usually forms between late childhood and early adulthood. In most cases, this enlargement does not cause the thyroid to malfunction.

In most people with Pendred syndrome, severe to profound hearing loss caused by changes in the inner ear (sensorineural hearing loss) is evident at birth. Less commonly, hearing loss does not develop until later in infancy or early childhood. Some affected individuals also have problems with balance caused by dysfunction of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation.

An inner ear abnormality called an enlarged vestibular aqueduct (EVA) is a characteristic feature of Pendred syndrome. The vestibular aqueduct is a bony canal that connects the inner ear with the inside of the skull. Some affected individuals also have an abnormally shaped cochlea, which is a snail-shaped structure in the inner ear that helps process sound. The combination of an enlarged vestibular aqueduct and an abnormally shaped cochlea is known as Mondini malformation.

Pendred syndrome shares features with other hearing loss and thyroid conditions, and it is unclear whether they are best considered as separate disorders or as a spectrum of related signs and symptoms. These conditions include a form of nonsyndromic hearing loss (hearing loss that does not affect other parts of the body) called DFNB4, and, in a small number of people, a form of congenital hypothyroidism resulting from an abnormally small thyroid gland (thyroid hypoplasia). All of these conditions are caused by mutations in the same gene.  https://medlineplus.gov/genetics/condition/pendred-syndrome

Clinical features

From HPO
Thyroid gland carcinoma
MedGen UID:
107811
Concept ID:
C0549473
Neoplastic Process
The presence of a carcinoma of the thyroid gland.
Abnormal vestibular function
MedGen UID:
334848
Concept ID:
C1843865
Finding
An abnormality of the functioning of the vestibular apparatus.
Cochlear malformation
MedGen UID:
396278
Concept ID:
C1862050
Finding
The presence of a malformed cochlea.
Congenital sensorineural hearing impairment
MedGen UID:
356101
Concept ID:
C1865866
Disease or Syndrome
A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Increased circulating thyroglobulin concentration
MedGen UID:
1375023
Concept ID:
C4476805
Finding
An abnormal elevation of the concentration of thyroglobulin, a protein produced in the thyroid gland that acts as a precursor to thyrroid hormones.
Goiter
MedGen UID:
42270
Concept ID:
C0018021
Disease or Syndrome
An enlargement of the thyroid gland.
Compensated hypothyroidism
MedGen UID:
473011
Concept ID:
C0271790
Disease or Syndrome
Condition associated with a raised serum concentration of thyroid stimulating hormone (TSH) but a normal serum free thyroxine (FT4).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPendred syndrome
Follow this link to review classifications for Pendred syndrome in Orphanet.

Professional guidelines

PubMed

Tawalbeh M, Aburizeg D, Abu Alragheb BO, Alaqrabawi WS, Dardas Z, Srour L, Altarayra BH, Zayed AA, El Omari Z, Azab B
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Recent clinical studies

Etiology

Skrivan J, Jurovcik M, Aksenovova Z, Astl J, Pourova RK, Dytrych P, Sieger T
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Otol Neurotol 2021 Oct 1;42(9):e1327-e1332. doi: 10.1097/MAO.0000000000003270. PMID: 34224544
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J Med Genet 2005 May;42(5):379-89. doi: 10.1136/jmg.2004.024158. PMID: 15863666Free PMC Article

Diagnosis

Lewis M, Robson CD, D'Arco F
Neuroimaging Clin N Am 2023 Nov;33(4):563-580. Epub 2023 Jul 4 doi: 10.1016/j.nic.2023.05.007. PMID: 37741658
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Wémeau JL, Kopp P
Best Pract Res Clin Endocrinol Metab 2017 Mar;31(2):213-224. Epub 2017 May 10 doi: 10.1016/j.beem.2017.04.011. PMID: 28648509
Glaser B
Pediatr Endocrinol Rev 2003 Dec;1 Suppl 2:199-204; discussion 204. PMID: 16444159

Therapy

Friis IJ, Aaberg K, Edholm B
Int J Pediatr Otorhinolaryngol 2023 Aug;171:111640. Epub 2023 Jul 1 doi: 10.1016/j.ijporl.2023.111640. PMID: 37441990
Chiarella G, Russo D, Monzani F, Petrolo C, Fattori B, Pasqualetti G, Cassandro E, Costante G
Endocr Pract 2017 Jul;23(7):863-868. Epub 2017 May 23 doi: 10.4158/EP161635.RA. PMID: 28534686
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J Endocrinol Invest 2011 Sep;34(8):593-8. Epub 2010 Sep 9 doi: 10.3275/7262. PMID: 20834201
Pela I, Bigozzi M, Bianchi B
Clin Nephrol 2008 Jun;69(6):450-3. doi: 10.5414/cnp69450. PMID: 18538122

Prognosis

Huang CJ, Jap TS
J Chin Med Assoc 2015 Mar;78(3):145-53. Epub 2014 Nov 11 doi: 10.1016/j.jcma.2014.09.010. PMID: 25455162
Dossena S, Nofziger C, Tamma G, Bernardinelli E, Vanoni S, Nowak C, Grabmayer E, Kössler S, Stephan S, Patsch W, Paulmichl M
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Clinical prediction guides

Forli F, Lazzerini F, Auletta G, Bruschini L, Berrettini S
Eur Arch Otorhinolaryngol 2021 Jul;278(7):2305-2312. Epub 2020 Sep 10 doi: 10.1007/s00405-020-06333-9. PMID: 32910226Free PMC Article
Wémeau JL, Kopp P
Best Pract Res Clin Endocrinol Metab 2017 Mar;31(2):213-224. Epub 2017 May 10 doi: 10.1016/j.beem.2017.04.011. PMID: 28648509
Chiarella G, Russo D, Monzani F, Petrolo C, Fattori B, Pasqualetti G, Cassandro E, Costante G
Endocr Pract 2017 Jul;23(7):863-868. Epub 2017 May 23 doi: 10.4158/EP161635.RA. PMID: 28534686
Dossena S, Nofziger C, Tamma G, Bernardinelli E, Vanoni S, Nowak C, Grabmayer E, Kössler S, Stephan S, Patsch W, Paulmichl M
Cell Physiol Biochem 2011;28(3):451-66. Epub 2011 Nov 18 doi: 10.1159/000335107. PMID: 22116358
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Recent systematic reviews

Hansen MU, Rye Rasmussen E, Cayé-Thomasen P, Mey K
Ear Hear 2023 May-Jun 01;44(3):440-447. Epub 2022 Nov 18 doi: 10.1097/AUD.0000000000001309. PMID: 36397213
Biggs K, Lovett A, Metcalfe C, Muzaffar J, Monksfield P, Bance M
J Int Adv Otol 2020 Dec;16(3):432-442. doi: 10.5152/iao.2020.9039. PMID: 33136026Free PMC Article
Huang CJ, Jap TS
J Chin Med Assoc 2015 Mar;78(3):145-53. Epub 2014 Nov 11 doi: 10.1016/j.jcma.2014.09.010. PMID: 25455162
Noordman BJ, van Beeck Calkoen E, Witte B, Goverts T, Hensen E, Merkus P
Otol Neurotol 2015 Jan;36(1):4-11. doi: 10.1097/MAO.0000000000000659. PMID: 25406869

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