Download PDF
Semin Hear 2006; 27(3): 160-170
DOI: 10.1055/s-2006-947283
Published in 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Pendred Syndrome

Anne C. Madeo1 , 6 , Shannon P. Pryor2 , 6 , Carmen Brewer3 , 6 , Christopher Zalewski4 , 6 , Kelly King5 , 6 , John A. Butman7 , Yandan Yang6 , 8 , Hong-Joon Park9 , Andrew J. Griffith6 , 10
  • 1Genetic Counselor
  • 2Chief, Clinical Otolaryngology
  • 3Chief, Audiology
  • 4Audiologist
  • 5Research Assistant
  • 6National Institutes of Health, Bethesda, Maryland
  • 7Senior Staff Clinician, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland
  • 8Biologist, Laboratory on Gene Structure and Function
  • 9Chief, Soree Ear Clinic, Seoul, Korea
  • 10Chief, Hearing Section
Further Information

Publication History

Publication Date:
17 July 2006 (online)

    Permissions and Reprints

ABSTRACT

Hearing loss with an onset in the pre- or perilingual period is a common feature of many hearing loss syndromes, including Pendred syndrome (PS). Although first identified over 100 years ago, PS remains a diagnostic challenge for many clinicians. Its hallmark features include inner ear malformations, most commonly enlarged vestibular aqueducts (EVA), prelingual onset hearing loss and goiter, or enlargement of the thyroid gland. However, these features are not found in all patients with PS, and sometimes they are found in individuals whose clinical evaluations are not consistent with PS. A combination of thorough clinical evaluations and appropriate genetic testing can, however, usually provide an accurate diagnosis. This article presents information on PS, nonsyndromic hearing loss with EVA, the etiology and molecular aspects of these disorders, their epidemiology in various ethnic populations, and their distinguishing clinical and genetic features.

KEYWORDS

Pendred syndrome - enlarged vestibular aqueducts - SLC26A4 - PDS - hearing loss

REFERENCES

  • 1 Pendred V. Deaf-Mutism and Goitre.  Lancet. 1896;  ii 532
    PubMedGoogle Scholar
  • 2 Coucke P, Van Camp G, Demirhan O et al.. The gene for Pendred syndrome is located between D7S501 and D7S692 in a 1.7-cM region on chromosome 7q.  Genomics. 1997;  40 48-54
    CrossrefPubMedGoogle Scholar
  • 3 Everett L A, Glaser B, Beck J C et al.. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).  Nat Genet. 1997;  17 411-422
    CrossrefPubMedGoogle Scholar
  • 4 Wain H M, Bruford E A, Lovering R C, Lush M J, Wright M W, Povey S. Guidelines for human gene nomenclature.  Genomics. 2002;  79 464-470
    CrossrefPubMedGoogle Scholar
  • 5 Ahmed Z M, Riazuddin S, Wilcox E R. The molecular genetics of Usher syndrome.  Clin Genet. 2003;  63 431-444
    CrossrefPubMedGoogle Scholar
  • 6 Karet F E. Inherited distal renal tubular acidosis.  J Am Soc Nephrol. 2002;  13 2178-2184
    CrossrefPubMedGoogle Scholar
  • 7 Bitner-Glindzicz M, Tranebjaerg L. The Jervell and Lange-Nielsen syndrome.  Adv Otorhinolaryngol. 2000;  56 45-52
    PubMedGoogle Scholar
  • 8 Schultz J. Waardenburg syndrome.  Semin Hear. 2006;  27 171-181
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Kalatzis V, Petit C. Branchio-oto-renal syndrome.  Adv Otorhinolaryngol. 2000;  56 39-44
    PubMedGoogle Scholar
  • 10 Hudson B G, Tryggvason K, Sundaramoorthy M, Neilson E G. Alport's syndrome, Goodpasture's syndrome, and type IV collagen.  N Engl J Med. 2003;  348 2543-2556
    CrossrefPubMedGoogle Scholar
  • 11 Pryor S P, Demmler G J, Madeo A C et al.. Investigation of the role of congenital cytomegalovirus infection in the etiology of enlarged vestibular aqueducts.  Arch Otolaryngol Head Neck Surg. 2005;  131 388-392
    CrossrefPubMedGoogle Scholar
  • 12 Scott D A, Wang R, Kreman T M, Sheffield V C, Karniski L P. The Pendred syndrome gene encodes a chloride-iodide transport protein.  Nat Genet. 1999;  21 440-443
    PubMedGoogle Scholar
  • 13 Scott D A, Karniski L P. Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange.  Am J Physiol Cell Physiol. 2000;  278 C207-C211
    PubMedGoogle Scholar
  • 14 Scott D A, Wang R, Kreman T M et al.. Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4).  Hum Mol Genet. 2000;  9 1709-1715
    CrossrefPubMedGoogle Scholar
  • 15 Fraser G R. Association of congenital deafness with goitre (Pendred's syndrome): a study of 207 families.  Ann Hum Genet. 1965;  28 201-249
    PubMedGoogle Scholar
  • 16 Fraser G R. Deafness with Goiter (Pendred's Syndrome). Baltimore, MD; The Johns Hopkins University Press 1976
    Google Scholar
  • 17 Reardon W, Coffey R, Phelps P D et al.. Pendred syndrome-100 years of underascertainment?.  QJM. 1997;  90 443-447
    CrossrefPubMedGoogle Scholar
  • 18 Park H J, Shaukat S, Liu X Z et al.. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness.  J Med Genet. 2003;  40 242-248
    CrossrefPubMedGoogle Scholar
  • 19 Reardon W, Coffey R, Chowdhury T et al.. Prevalence, age of onset, and natural history of thyroid disease in Pendred syndrome.  J Med Genet. 1999;  36 595-598
    PubMedGoogle Scholar
  • 20 Johnsen T, Larsen C, Friis J, Hougaard-Jensen F. Pendred's syndrome. Acoustic, vestibular and radiological findings in 17 unrelated patients.  J Laryngol Otol. 1987;  101 1187-1192
    PubMedGoogle Scholar
  • 21 Morgans M E, Trotter W R. Association of congenital deafness with goitre: the nature of the thyroid defect.  Lancet. 1958;  i 607-609
    CrossrefPubMedGoogle Scholar
  • 22 Jamal M N, Arnaout M A, Jarrar R. Pendred's syndrome: a study of patients and relatives.  Ann Otol Rhinol Laryngol. 1995;  104 957-962
    PubMedGoogle Scholar
  • 23 Phelps P D, Coffey R A, Trembath R C et al.. Radiological malformations of the ear in Pendred syndrome.  Clin Radiol. 1998;  53 268-273
    PubMedGoogle Scholar
  • 24 Andersen P E. Radiology of Pendred's syndrome.  Adv Otorhinolaryngol. 1974;  21 9-18
    PubMedGoogle Scholar
  • 25 Sennaroglu L, Saatci I. Unpartitioned versus incompletely partitioned cochleae: radiologic differentiation.  Otol Neurotol. 2004;  25 520-529 , discussion 529
    CrossrefPubMedGoogle Scholar
  • 26 Valvassori G E, Clemis J D. The large vestibular aqueduct syndrome.  Laryngoscope. 1978;  88 723-728
    CrossrefPubMedGoogle Scholar
  • 27 Govaerts P J, Casselman J, Daemers K, De Ceulaer G, Somers T, Offeciers F E. Audiological findings in large vestibular aqueduct syndrome.  Int J Pediatr Otorhinolaryngol. 1999;  51 157-164
    CrossrefPubMedGoogle Scholar
  • 28 Cremers C W, Admiraal R J, Huygen P L et al.. Progressive hearing loss, hypoplasia of the cochlea and widened vestibular aqueducts are very common features in Pendred's syndrome.  Int J Pediatr Otorhinolaryngol. 1998;  45 113-123
    CrossrefPubMedGoogle Scholar
  • 29 Arjmand E M, Webber A. Audiometric findings in children with a large vestibular aqueduct.  Arch Otolaryngol Head Neck Surg. 2004;  130 1169-1174
    CrossrefPubMedGoogle Scholar
  • 30 Nakashima T, Ueda H, Furuhashi A et al.. Air-bone gap and resonant frequency in large vestibular aqueduct syndrome.  Am J Otol. 2000;  21 671-674
    PubMedGoogle Scholar
  • 31 Sato E, Nakashima T, Lilly D J et al.. Tympanometric findings in patients with enlarged vestibular aqueducts.  Laryngoscope. 2002;  112 1642-1646
    PubMedGoogle Scholar
  • 32 Mimura T, Sato E, Sugiura M, Yoshino T, Naganawa S, Nakashima T. Hearing loss in patients with enlarged vestibular aqueduct: air-bone gap and audiological Bing test.  Int J Audiol. 2005;  44 466-469
    PubMedGoogle Scholar
  • 33 Stinckens C, Huygen P L, Joosten F B, Van Camp G, Otten B, Cremers C W. Fluctuant, progressive hearing loss associated with Meniere-like vertigo in three patients with the Pendred syndrome.  Int J Pediatr Otorhinolaryngol. 2001;  61 207-215
    CrossrefPubMedGoogle Scholar
  • 34 Iwasaki S, Usami S, Abe S, Isoda H, Watanabe T, Hoshino T. Long-term audiological feature in Pendred syndrome caused by PDS mutation.  Arch Otolaryngol Head Neck Surg. 2001;  127 705-708
    PubMedGoogle Scholar
  • 35 Abe S, Usami S, Hoover D M, Cohn E, Shinkawa H, Kimberling W J. Fluctuating sensorineural hearing loss associated with enlarged vestibular aqueduct maps to 7q31, the region containing the Pendred gene.  Am J Med Genet. 1999;  82 322-328
    CrossrefPubMedGoogle Scholar
  • 36 Luxon L M, Cohen M, Coffey R A et al.. Neuro-otological findings in Pendred syndrome.  Int J Audiol. 2003;  42 82-88
    PubMedGoogle Scholar
  • 37 Bergstrom L. Pendred's syndrome with atypical features.  Ann Otol Rhinol Laryngol. 1980;  89 (2 Pt 1) 135-139
    PubMedGoogle Scholar
  • 38 Das V K. Pendred's syndrome with episodic vertigo, tinnitus and vomiting and normal bithermal caloric responses.  J Laryngol Otol. 1987;  101 721-722
    PubMedGoogle Scholar
  • 39 Griffith A J, Arts A, Downs C et al.. Familial large vestibular aqueduct syndrome.  Laryngoscope. 1996;  106 960-965
    PubMedGoogle Scholar
  • 40 Ramirez-Camacho R, Berrocal J RG, Arellano B, Trinidad A. Familial isolated unilateral large vestibular aqueduct syndrome.  ORL J Otorhinolaryngol Relat Spec. 2003;  65 45-48
    PubMedGoogle Scholar
  • 41 Madden C, Halsted M, Benton C, Greinwald J, Choo D. Enlarged vestibular aqueduct syndrome in the pediatric population.  Otol Neurotol. 2003;  24 625-632
    PubMedGoogle Scholar
  • 42 Lai C C, Shiao A S. Chronological changes of hearing in pediatric patients with large vestibular aqueduct syndrome.  Laryngoscope. 2004;  114 832-838
    CrossrefPubMedGoogle Scholar
  • 43 Swartz J D. An overview of congenital/developmental sensorineural hearing loss with emphasis on the vestibular aqueduct syndrome.  Semin Ultrasound CT MR. 2004;  25 353-368
    CrossrefPubMedGoogle Scholar
  • 44 Kopp P, Arseven O K, Sabacan L et al.. Phenocopies for deafness and goiter development in a large inbred Brazilian kindred with Pendred's syndrome associated with a novel mutation in the PDS gene.  J Clin Endocrinol Metab. 1999;  84 336-341
    CrossrefPubMedGoogle Scholar
  • 45 Campbell C, Cucci R A, Prasad S et al.. Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.  Hum Mutat. 2001;  17 403-411
    CrossrefPubMedGoogle Scholar
  • 46 Coyle B, Reardon W, Herbrick J A et al.. Molecular analysis of the PDS gene in Pendred syndrome.  Hum Mol Genet. 1998;  7 1105-1112
    CrossrefPubMedGoogle Scholar
  • 47 Gonzalez Trevino O, Karamanoglu Arseven O, Ceballos C J et al.. Clinical and molecular analysis of three Mexican families with Pendred's syndrome.  Eur J Endocrinol. 2001;  144 585-593
    CrossrefPubMedGoogle Scholar
  • 48 Pryor S P, Madeo A C, Reynolds J C et al.. SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities.  J Med Genet. 2005;  42 159-165
    CrossrefPubMedGoogle Scholar
  • 49 Robin N H, Dietz C, Arnold J E, Smith R J. Pediatric otolaryngologists' knowledge and understanding of genetic testing for deafness.  Arch Otolaryngol Head Neck Surg. 2001;  127 937-940
    PubMedGoogle Scholar
  • 50 Kenen R H, Schmidt R M. Stigmatization of carrier status: social implications of heterozygote genetic screening programs.  Am J Public Health. 1978;  68 1116-1120
    PubMedGoogle Scholar
  • 51 Van Hauwe P, Everett L A, Coucke P et al.. Two frequent missense mutations in Pendred syndrome.  Hum Mol Genet. 1998;  7 1099-1104
    CrossrefPubMedGoogle Scholar
  • 52 Usami S, Abe S, Weston M D, Shinkawa H, Van Camp G, Kimberling W J. Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations.  Hum Genet. 1999;  104 188-192
    PubMedGoogle Scholar
  • 53 Kitamura K, Takahashi K, Noguchi Y et al.. Mutations of the Pendred syndrome gene (PDS) in patients with large vestibular aqueduct.  Acta Otolaryngol. 2000;  120 137-141
    CrossrefPubMedGoogle Scholar
  • 54 Borck G, Roth C, Martine U, Wildhardt G, Pohlenz J. Mutations in the PDS gene in German families with Pendred's syndrome: V138F is a founder mutation.  J Clin Endocrinol Metab. 2003;  88 2916-2921
    CrossrefPubMedGoogle Scholar
  • 55 Lopez-Bigas N, Rabionet R, de Cid R et al.. Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in Pendred syndrome.  Hum Mutat. 1999;  14 520-526
    CrossrefPubMedGoogle Scholar
  • 56 Tsukamoto K, Suzuki H, Harada D, Namba A, Abe S, Usami S. Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese.  Eur J Hum Genet. 2003;  11 916-922
    PubMedGoogle Scholar
  • 57 Blons H, Feldmann D, Duval V et al.. Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity.  Clin Genet. 2004;  66 333-340
    CrossrefPubMedGoogle Scholar
  • 58 Wu C C, Yeh T H, Chen P J, Hsu C J. Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation.  Laryngoscope. 2005;  115 1060-1064
    CrossrefPubMedGoogle Scholar
  • 59 Park H J, Lee S J, Jin H S et al.. Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans.  Clin Genet. 2005;  67 160-165
    CrossrefPubMedGoogle Scholar
  • 60 Mafong D D, Shin E J, Lalwani A K. Use of laboratory evaluation and radiologic imaging in the diagnostic evaluation of children with sensorineural hearing loss.  Laryngoscope. 2002;  112 1-7
    PubMedGoogle Scholar
  • 61 Preciado D A, Lawson L, Madden C et al.. Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss.  Otol Neurotol. 2005;  26 610-615
    CrossrefPubMedGoogle Scholar
  • 62 Genetic Evaluation of Congenital Hearing Loss Expert Panel . Genetics evaluation guidelines for the etiologic diagnosis of congenital hearing loss. ACMG statement.  Genet Med. 2002;  4 162-171
    PubMedGoogle Scholar
  • 63 NIH Consensus Conference . Cochlear implants in adults and children.  JAMA. 1995;  274 1955-1961
    CrossrefPubMedGoogle Scholar
  • 64 Fahy C P, Carney A S, Nikolopoulos T P, Ludman C N, Gibbin K P. Cochlear implantation in children with large vestibular aqueduct syndrome and a review of the syndrome.  Int J Pediatr Otorhinolaryngol. 2001;  59 207-215
    CrossrefPubMedGoogle Scholar
  • 65 Miyamoto R T, Bichey B G, Wynne M K, Kirk K I. Cochlear implantation with large vestibular aqueduct syndrome.  Laryngoscope. 2002;  112(7 Pt 1) 1178-1182
    CrossrefPubMedGoogle Scholar
  • 66 Mylanus E A, Rotteveel L J, Leeuw R L. Congenital malformation of the inner ear and pediatric cochlear implantation.  Otol Neurotol. 2004;  25 308-317
    PubMedGoogle Scholar
  • 67 Jackler R K, De La Cruz A. The large vestibular aqueduct syndrome.  Laryngoscope. 1989;  99 1238-1242
    PubMedGoogle Scholar
  • 68 Wilson D F, Hodgson R S, Talbot J M. Endolymphatic sac obliteration for large vestibular aqueduct syndrome.  Am J Otol. 1997;  18 101-107
    PubMedGoogle Scholar
  • 69 Everett L A, Belyantseva I A, Noben-Trauth K et al.. Targeted disruption of mouse PDS provides insight about the inner-ear defects encountered in Pendred syndrome.  Hum Mol Genet. 2001;  10 153-161
    CrossrefPubMedGoogle Scholar
  • 70 Illum P, Kiaer H W, Hvidberg-Hansen J, Sondergaard G. Fifteen cases of Pendred's syndrome. Congenital deafness and sporadic goiter.  Arch Otolaryngol. 1972;  96 297-304
    PubMedGoogle Scholar
  • 71 Everett L A, Morsli H, Wu D K, Green E D. Expression pattern of the mouse ortholog of the Pendred's syndrome gene (PDS) suggests a key role for pendrin in the inner ear.  Proc Natl Acad Sci USA. 1999;  96 9727-9732
    CrossrefPubMedGoogle Scholar
  • 72 Sheykholeslami K, Schmerber S, Habiby Kermany M, Kaga K. Vestibular-evoked myogenic potentials in three patients with large vestibular aqueduct.  Hear Res. 2004;  190(1-2) 161-168
    CrossrefPubMedGoogle Scholar
  • 73 Israel J. An Introduction to Deafness: a Manual for Genetic Counselors. Washington, DC; Gallaudet University and the National Society of Genetic Counselors Special Projects Fund 1995
    Google Scholar
  • 74 Rosenthal E T, Biesecker L G, Biesecker B B. Parental attitudes toward a diagnosis in children with unidentified multiple congenital anomaly syndromes.  Am J Med Genet. 2001;  103 106-114
    CrossrefPubMedGoogle Scholar
  • 75 Lenhard W, Breitenbach E, Ebert H, Schindelhauer-Deutscher H J, Henn W. Psychological benefit of diagnostic certainty for mothers of children with disabilities: lessons from Down syndrome.  Am J Med Genet A. 2005;  133 170-175
    PubMedGoogle Scholar

Anne C MadeoM.S. 

National Institutes of Health

9000 Rockville Pike, Bethesda, MD 20892

Email: Anne.Madeo@nih.gov

      >