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Hearing loss and renal syndromes

  • Educational Review
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Abstract

The association between ear and kidney abnormalities has long been recognized; however, the connection between these two disparate organs is not always straightforward. Although Alport syndrome is the most well-known, there are over 20 disorders that need to be considered in the differential diagnosis of patients with both ear and kidney abnormalities. Commonalities are present between the kidney and ear in a number of structural proteins, developmentally important transcription factors, ciliary proteins, and channel proteins, and mutations in these pathways can lead to disease in both organ systems. This manuscript reviews the congenital disorders with both hearing and kidney manifestations.

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References

  1. Sliwinska-Kowalska M (2015) Hearing. Handb Clin Neurol 131:341–363

    Article  PubMed  Google Scholar 

  2. Lang F, Vallon V, Knipper M, Wangemann P (2007) Functional significance of channels and transporters expressed in the inner ear and kidney. Am J Physiol Cell Physiol 293(4):C1187–C1208

    Article  PubMed  CAS  Google Scholar 

  3. Barker DF, Hostikka SL, Zhou J, Chow LT, Oliphant AR, Gerken SC, Gregory MC, Skolnick MH, Atkin CL, Tryggvason K (1990) Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science 248(4960):1224–1227

    Article  PubMed  CAS  Google Scholar 

  4. Mochizuki T, Lemmink HH, Mariyama M, Antignac C, Gubler MC, Pirson Y, Verellen-Dumoulin C, Chan B, Schroder CH, Smeets HJ, Reeders ST (1994) Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 8(1):77–81

    Article  PubMed  CAS  Google Scholar 

  5. Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Verellen C, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2000) X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 11 (4):649-657

  6. Storey H, Savige J, Sivakumar V, Abbs S, Flinter FA (2013) COL4A3/COL4A4 mutations and features in individuals with autosomal recessive Alport syndrome. J Am Soc Nephrol 24(12):1945–1954

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Marcocci E, Uliana V, Bruttini M, Artuso R, Silengo MC, Zerial M, Bergesio F, Amoroso A, Savoldi S, Pennesi M, Giachino D, Rombola G, Fogazzi GB, Rosatelli C, Martinhago CD, Carmellini M, Mancini R, Di Costanzo G, Longo I, Renieri A, Mari F (2009) Autosomal dominant Alport syndrome: molecular analysis of the COL4A4 gene and clinical outcome. Nephrol Dial Transplant 24 (5):1464–1471

  8. Rheault MN (2012) Women and Alport syndrome. Pediatr Nephrol 27(1):41–46

    Article  PubMed  Google Scholar 

  9. Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Dahan K, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2003) X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport syndrome concerted action” study. J Am Soc Nephrol 14(10):2603–2610

    Article  PubMed  Google Scholar 

  10. Kashtan CE, Ding J, Gregory M, Gross O, Heidet L, Knebelmann B, Rheault M, Licht C (2013) Clinical practice recommendations for the treatment of Alport syndrome: a statement of the Alport syndrome research collaborative. Pediatr Nephrol 28(1):5–11

    Article  PubMed  Google Scholar 

  11. Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tonshoff B, Hocker B, Wygoda S, Ehrich JH, Pape L, Konrad M, Rascher W, Dotsch J, Muller-Wiefel DE, Hoyer P, Knebelmann B, Pirson Y, Grunfeld JP, Niaudet P, Cochat P, Heidet L, Lebbah S, Torra R, Friede T, Lange K, Muller GA, Weber M (2012) Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 81(5):494–501

    Article  PubMed  CAS  Google Scholar 

  12. Wester DC, Atkin CL, Gregory MC (1995) Alport syndrome: clinical update. J Am Acad Audiol 6:73–79

    PubMed  CAS  Google Scholar 

  13. Kleppel MM, Santi PA, Cameron JD, Wieslander J, Michael AF (1989) Human tissue distribution of novel basement membrane collagen. Am J Pathol 134:813–825

    PubMed  PubMed Central  CAS  Google Scholar 

  14. Cosgrove D, Samuelson G, Meehan DT, Miller C, McGee J, Walsh EJ, Siegel M (1998) Ultrastructural, physiological, and molecular defects in the inner ear of a gene-knockout mouse model of autosomal Alport syndrome. Hearing Res 121:84–98

    Article  CAS  Google Scholar 

  15. Harvey SJ, Mount R, Sado Y, Naito I, Ninomiya Y, Harrison R, Jefferson B, Jacobs R, Thorner PS (2001) The inner ear of dogs with X-linked nephritis provides clues to the pathogenesis of hearing loss in X-linked Alport syndrome. Am J Pathol 159(3):1097–1104

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Seri M, Pecci A, Di Bari F, Cusano R, Savino M, Panza E, Nigro A, Noris P, Gangarossa S, Rocca B, Gresele P, Bizzaro N, Malatesta P, Koivisto PA, Longo I, Musso R, Pecoraro C, Iolascon A, Magrini U, Rodriguez Soriano J, Renieri A, Ghiggeri GM, Ravazzolo R, Balduini CL, Savoia A (2003) MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore) 82(3):203–215

    Google Scholar 

  17. Singh N, Nainani N, Arora P, Venuto RC (2009) CKD in MYH9-related disorders. Am J Kidney Dis 54(4):732–740

    Article  PubMed  CAS  Google Scholar 

  18. Naito I, Nomura S, Inoue S, Kagawa M, Kawai S, Gunshin Y, Joh K, Tsukidate C, Sado Y, Osawa G (1997) Normal distribution of collagen IV in renal basement membranes in Epstein’s syndrome. J Clin Pathol 50(11):919–922

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Pecci A, Klersy C, Gresele P, Lee KJ, De Rocco D, Bozzi V, Russo G, Heller PG, Loffredo G, Ballmaier M, Fabris F, Beggiato E, Kahr WH, Pujol-Moix N, Platokouki H, Van Geet C, Noris P, Yerram P, Hermans C, Gerber B, Economou M, De Groot M, Zieger B, De Candia E, Fraticelli V, Kersseboom R, Piccoli GB, Zimmermann S, Fierro T, Glembotsky AC, Vianello F, Zaninetti C, Nicchia E, Guthner C, Baronci C, Seri M, Knight PJ, Balduini CL, Savoia A (2014) MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations. Hum Mutat 35 (2):236-247

  20. Mhatre AN, Li J, Kim Y, Coling DE, Lalwani AK (2004) Cloning and developmental expression of nonmuscle myosin IIA (Myh9) in the mammalian inner ear. J Neurosci Res 76(3):296–305

    Article  PubMed  CAS  Google Scholar 

  21. Suntjens EB, Smid BE, Biegstraaten M, Dreschler WA, Hollak CE, Linthorst GE (2015) Hearing loss in adult patients with Fabry disease treated with enzyme replacement therapy. J Inherit Metab Dis 38(2):351–358

    Article  PubMed  CAS  Google Scholar 

  22. Suntjens E, Dreschler WA, Hess-Erga J, Skrunes R, Wijburg FA, Linthorst GE, Tondel C, Biegstraaten M (2017) Hearing loss in children with Fabry disease. J Inherit Metab Dis. doi: 10.1007/s10545-017-0051-5

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sakurai Y, Suzuki R, Yoshida R, Kojima H, Watanabe M, Manome Y, Ohashi T, Eto Y, Moriyama H (2010) Inner ear pathology of alpha-galactosidase A deficient mice, a model of Fabry disease. Auris Nasus Larynx 37(3):274–280

    Article  PubMed  Google Scholar 

  24. Schachern PA, Shea DA, Paparella MM, Yoon TH (1989) Otologic histopathology of Fabry’s disease. Ann Otol Rhinol Laryngol 98(5 Pt 1):359–363

    Article  PubMed  CAS  Google Scholar 

  25. Rossor AM, Polke JM, Houlden H, Reilly MM (2013) Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat Rev Neurol 9(10):562–571

    Article  PubMed  CAS  Google Scholar 

  26. Boyer O, Nevo F, Plaisier E, Funalot B, Gribouval O, Benoit G, Huynh Cong E, Arrondel C, Tete MJ, Montjean R, Richard L, Karras A, Pouteil-Noble C, Balafrej L, Bonnardeaux A, Canaud G, Charasse C, Dantal J, Deschenes G, Deteix P, Dubourg O, Petiot P, Pouthier D, Leguern E, Guiochon-Mantel A, Broutin I, Gubler MC, Saunier S, Ronco P, Vallat JM, Alonso MA, Antignac C, Mollet G (2011) INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy. N Engl J Med 365(25):2377–2388

    Article  PubMed  CAS  Google Scholar 

  27. Muller U, Littlewood-Evans A (2001) Mechanisms that regulate mechanosensory hair cell differentiation. Trends Cell Biol 11(8):334–342

    Article  PubMed  CAS  Google Scholar 

  28. Diomedi-Camassei F, Di Giandomenico S, Santorelli FM, Caridi G, Piemonte F, Montini G, Ghiggeri GM, Murer L, Barisoni L, Pastore A, Muda AO, Valente ML, Bertini E, Emma F (2007) COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J Am Soc Nephrol 18(10):2773–2780

    Article  PubMed  CAS  Google Scholar 

  29. Heeringa SF, Chernin G, Chaki M, Zhou W, Sloan AJ, Ji Z, Xie LX, Salviati L, Hurd TW, Vega-Warner V, Killen PD, Raphael Y, Ashraf S, Ovunc B, Schoeb DS, McLaughlin HM, Airik R, Vlangos CN, Gbadegesin R, Hinkes B, Saisawat P, Trevisson E, Doimo M, Casarin A, Pertegato V, Giorgi G, Prokisch H, Rotig A, Nurnberg G, Becker C, Wang S, Ozaltin F, Topaloglu R, Bakkaloglu A, Bakkaloglu SA, Muller D, Beissert A, Mir S, Berdeli A, Varpizen S, Zenker M, Matejas V, Santos-Ocana C, Navas P, Kusakabe T, Kispert A, Akman S, Soliman NA, Krick S, Mundel P, Reiser J, Nurnberg P, Clarke CF, Wiggins RC, Faul C, Hildebrandt F (2011) COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J Clin Invest 121(5):2013–2024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Salviati L, Sacconi S, Murer L, Zacchello G, Franceschini L, Laverda AM, Basso G, Quinzii C, Angelini C, Hirano M, Naini AB, Navas P, DiMauro S, Montini G (2005) Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition. Neurology 65(4):606–608

    Article  PubMed  CAS  Google Scholar 

  31. Doimo M, Desbats MA, Cerqua C, Cassina M, Trevisson E, Salviati L (2014) Genetics of coenzyme q10 deficiency. Mol Syndromol 5(3–4):156–162

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Kurogouchi F, Oguchi T, Mawatari E, Yamaura S, Hora K, Takei M, Sekijima Y, Ikeda S, Kiyosawa K (1998) A case of mitochondrial cytopathy with a typical point mutation for MELAS, presenting with severe focal-segmental glomerulosclerosis as main clinical manifestation. Am J Nephrol 18(6):551–556

    Article  PubMed  CAS  Google Scholar 

  33. Yorifuji T, Kawai M, Momoi T, Sasaki H, Furusho K, Muroi J, Shimizu K, Takahashi Y, Matsumura M, Nambu M, Okuno T (1996) Nephropathy and growth hormone deficiency in a patient with mitochondrial tRNA(Leu(UUR)) mutation. J Med Genet 33(7):621–622

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Ding Y, Leng J, Fan F, Xia B, Xu P (2013) The role of mitochondrial DNA mutations in hearing loss. Biochem Genet 51(7–8):588–602

    Article  PubMed  CAS  Google Scholar 

  35. Karikkineth AC, Scheibye-Knudsen M, Fivenson E, Croteau DL, Bohr VA (2017) Cockayne syndrome: clinical features, model systems and pathways. Ageing Res Rev 33:3–17. https://doi.org/10.1016/j.arr.2016.08.002

    Article  PubMed  CAS  Google Scholar 

  36. Hirooka M, Hirota M, Kamada M (1988) Renal lesions in Cockayne syndrome. Pediatr Nephrol 2(2):239–243

    Article  PubMed  CAS  Google Scholar 

  37. Wilson BT, Stark Z, Sutton RE, Danda S, Ekbote AV, Elsayed SM, Gibson L, Goodship JA, Jackson AP, Keng WT, King MD, McCann E, Motojima T, Murray JE, Omata T, Pilz D, Pope K, Sugita K, White SM, Wilson IJ (2016) The Cockayne syndrome natural history (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. Genet Med 18(5):483–493

    Article  PubMed  Google Scholar 

  38. Kagan A, Feld S, Chemke J, Bar-Khayim Y (1988) Occurrence of hereditary nephritis, pretibial epidermolysis bullosa and beta-thalassemia minor in two siblings with end-stage renal disease. Nephron 49(4):331–332

    Article  PubMed  CAS  Google Scholar 

  39. Karamatic Crew V, Burton N, Kagan A, Green CA, Levene C, Flinter F, Brady RL, Daniels G, Anstee DJ (2004) CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood 104(8):2217–2223

    Article  PubMed  CAS  Google Scholar 

  40. Tran TA (2017) Muckle-Wells syndrome: clinical perspectives. Open Access Rheumatol 9:123–129

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kuemmerle-Deschner JB, Koitschev A, Tyrrell PN, Plontke SK, Deschner N, Hansmann S, Ummenhofer K, Lohse P, Koitschev C, Benseler SM (2015) Early detection of sensorineural hearing loss in Muckle-Wells-syndrome. Pediatr Rheumatol Online J 13(1):43

    Article  PubMed  PubMed Central  Google Scholar 

  42. Fraser FC, Sproule JR, Halal F (1980) Frequency of the branchio-oto-renal (BOR) syndrome in children with profound hearing loss. Am J Med Genet 7(3):341–349

    Article  PubMed  CAS  Google Scholar 

  43. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, Weil D, Cruaud C, Sahly I, Leibovici M, Bitner-Glindzicz M, Francis M, Lacombe D, Vigneron J, Charachon R, Boven K, Bedbeder P, Van Regemorter N, Weissenbach J, Petit C (1997) A human homologue of the drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet 15(2):157–164

    Article  PubMed  CAS  Google Scholar 

  44. Ruf RG, Xu PX, Silvius D, Otto EA, Beekmann F, Muerb UT, Kumar S, Neuhaus TJ, Kemper MJ, Raymond RM Jr, Brophy PD, Berkman J, Gattas M, Hyland V, Ruf EM, Schwartz C, Chang EH, Smith RJ, Stratakis CA, Weil D, Petit C, Hildebrandt F (2004) SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci U S A 101(21):8090–8095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Hoskins BE, Cramer CH, Silvius D, Zou D, Raymond RM, Orten DJ, Kimberling WJ, Smith RJ, Weil D, Petit C, Otto EA, Xu PX, Hildebrandt F (2007) Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. Am J Hum Genet 80(4):800–804

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Mutsuddi M, Chaffee B, Cassidy J, Silver SJ, Tootle TL, Rebay I (2005) Using drosophila to decipher how mutations associated with human branchio-oto-renal syndrome and optical defects compromise the protein tyrosine phosphatase and transcriptional functions of eyes absent. Genetics 170(2):687–695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Kalatzis V, Sahly I, El-Amraoui A, Petit C (1998) Eya1 expression in the developing ear and kidney: towards the understanding of the pathogenesis of branchio-oto-renal (BOR) syndrome. Dev Dyn 213(4):486–499

    Article  PubMed  CAS  Google Scholar 

  48. Chang EH, Menezes M, Meyer NC, Cucci RA, Vervoort VS, Schwartz CE, Smith RJ (2004) Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences. Hum Mutat 23(6):582–589

    Article  PubMed  CAS  Google Scholar 

  49. Kochhar A, Fischer SM, Kimberling WJ, Smith RJ (2007) Branchio-oto-renal syndrome. Am J Med Genet A 143A(14):1671–1678

    Article  PubMed  CAS  Google Scholar 

  50. Powell CM, Michaelis RC (1999) Townes-Brocks syndrome. J Med Genet 36(2):89–93

    PubMed  PubMed Central  CAS  Google Scholar 

  51. Nishinakamura R, Matsumoto Y, Nakao K, Nakamura K, Sato A, Copeland NG, Gilbert DJ, Jenkins NA, Scully S, Lacey DL, Katsuki M, Asashima M, Yokota T (2001) Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development 128(16):3105–3115

    PubMed  CAS  Google Scholar 

  52. Botzenhart EM, Bartalini G, Blair E, Brady AF, Elmslie F, Chong KL, Christy K, Torres-Martinez W, Danesino C, Deardorff MA, Fryns JP, Marlin S, Garcia-Minaur S, Hellenbroich Y, Hay BN, Penttinen M, Shashi V, Terhal P, Van Maldergem L, Whiteford ML, Zackai E, Kohlhase J (2007) Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region. Hum Mutat 28(2):204–205

    Article  PubMed  Google Scholar 

  53. Ferraz FG, Nunes L, Ferraz ME, Sousa JP, Santos M, Carvalho C, Maroteaux P (1989) Townes-Brocks syndrome. Report of a case and review of the literature. Ann Genet 32(2):120–123

    PubMed  CAS  Google Scholar 

  54. Kohlhase J, Wischermann A, Reichenbach H, Froster U, Engel W (1998) Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. Nat Genet 18(1):81–83

    Article  PubMed  CAS  Google Scholar 

  55. Janssen N, Bergman JE, Swertz MA, Tranebjaerg L, Lodahl M, Schoots J, Hofstra RM, van Ravenswaaij-Arts CM, Hoefsloot LH (2012) Mutation update on the CHD7 gene involved in CHARGE syndrome. Hum Mutat 33(8):1149–1160

    Article  PubMed  CAS  Google Scholar 

  56. Lalani SR, Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW (2004) SEMA3E mutation in a patient with CHARGE syndrome. J Med Genet 41(7):e94

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Hsu P, Ma A, Wilson M, Williams G, Curotta J, Munns CF, Mehr S (2014) CHARGE syndrome: a review. J Paediatr Child Health 50(7):504–511

    Article  PubMed  Google Scholar 

  58. Pauws E, Peskett E, Boissin C, Hoshino A, Mengrelis K, Carta E, Abruzzo MA, Lees M, Moore GE, Erickson RP, Stanier P (2013) X-linked CHARGE-like Abruzzo-Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations. Clin Genet 83(4):352–358

    Article  PubMed  CAS  Google Scholar 

  59. Abruzzo MA, Erickson RP (1977) A new syndrome of cleft palate associated with coloboma, hypospadias, deafness, short stature, and radial synostosis. J Med Genet 14(1):76–80

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Bergmann C (2012) Educational paper: ciliopathies. Eur J Pediatr 171(9):1285–1300

    Article  PubMed  Google Scholar 

  61. Hildebrandt F, Benzing T, Katsanis N (2011) Ciliopathies. N Engl J Med 364(16):1533–1543

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Forsythe E, Beales PL (2013) Bardet-Biedl syndrome. Eur J Hum Genet 21(1):8–13

    Article  PubMed  CAS  Google Scholar 

  63. Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA (1999) New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet 36(6):437–446

    PubMed  PubMed Central  CAS  Google Scholar 

  64. Ross AJ, May-Simera H, Eichers ER, Kai M, Hill J, Jagger DJ, Leitch CC, Chapple JP, Munro PM, Fisher S, Tan PL, Phillips HM, Leroux MR, Henderson DJ, Murdoch JN, Copp AJ, Eliot MM, Lupski JR, Kemp DT, Dollfus H, Tada M, Katsanis N, Forge A, Beales PL (2005) Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 37(10):1135–1140

    Article  PubMed  CAS  Google Scholar 

  65. Forsythe E, Sparks K, Best S, Borrows S, Hoskins B, Sabir A, Barrett T, Williams D, Mohammed S, Goldsmith D, Milford DV, Bockenhauer D, Foggensteiner L, Beales PL (2017) Risk factors for severe renal disease in Bardet-Biedl syndrome. J Am Soc Nephrol 28(3):963–970

    Article  PubMed  Google Scholar 

  66. Katsanis N, Beales PL, Woods MO, Lewis RA, Green JS, Parfrey PS, Ansley SJ, Davidson WS, Lupski JR (2000) Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome. Nat Genet 26(1):67–70

    Article  PubMed  CAS  Google Scholar 

  67. Marshall JD, Hinman EG, Collin GB, Beck S, Cerqueira R, Maffei P, Milan G, Zhang W, Wilson DI, Hearn T, Tavares P, Vettor R, Veronese C, Martin M, So WV, Nishina PM, Naggert JK (2007) Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome. Hum Mutat 28(11):1114–1123

    Article  PubMed  CAS  Google Scholar 

  68. May-Simera H (2016) Evaluation of planar-cell-polarity phenotypes in Ciliopathy mouse mutant cochlea. J Vis Exp 108:53559

    Google Scholar 

  69. Marshall JD, Bronson RT, Collin GB, Nordstrom AD, Maffei P, Paisey RB, Carey C, Macdermott S, Russell-Eggitt I, Shea SE, Davis J, Beck S, Shatirishvili G, Mihai CM, Hoeltzenbein M, Pozzan GB, Hopkinson I, Sicolo N, Naggert JK, Nishina PM (2005) New Alstrom syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med 165(6):675–683

    Article  PubMed  Google Scholar 

  70. Koulouridis E, Koulouridis I (2015) Molecular pathophysiology of Bartter’s and Gitelman’s syndromes. World J Pediatr 11(2):113–125

    Article  PubMed  CAS  Google Scholar 

  71. Janssen AG, Scholl U, Domeyer C, Nothmann D, Leinenweber A, Fahlke C (2009) Disease-causing dysfunctions of barttin in Bartter syndrome type IV. J Am Soc Nephrol 20(1):145–153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Birkenhager R, Otto E, Schurmann MJ, Vollmer M, Ruf EM, Maier-Lutz I, Beekmann F, Fekete A, Omran H, Feldmann D, Milford DV, Jeck N, Konrad M, Landau D, Knoers NV, Antignac C, Sudbrak R, Kispert A, Hildebrandt F (2001) Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet 29(3):310–314

    Article  PubMed  CAS  Google Scholar 

  73. Estevez R, Boettger T, Stein V, Birkenhager R, Otto E, Hildebrandt F, Jentsch TJ (2001) Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion. Nature 414(6863):558–561

    Article  PubMed  CAS  Google Scholar 

  74. Schlingmann KP, Konrad M, Jeck N, Waldegger P, Reinalter SC, Holder M, Seyberth HW, Waldegger S (2004) Salt wasting and deafness resulting from mutations in two chloride channels. N Engl J Med 350(13):1314–1319

    Article  PubMed  CAS  Google Scholar 

  75. Doupnik CA, Davidson N, Lester HA (1995) The inward rectifier potassium channel family. Curr Opin Neurobiol 5(3):268–277

    Article  PubMed  CAS  Google Scholar 

  76. Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, Tobin J, Lieberer E, Sterner C, Landoure G, Arora R, Sirimanna T, Thompson D, Cross JH, van’t Hoff W, Al Masri O, Tullus K, Yeung S, Anikster Y, Klootwijk E, Hubank M, Dillon MJ, Heitzmann D, Arcos-Burgos M, Knepper MA, Dobbie A, Gahl WA, Warth R, Sheridan E, Kleta R (2009) Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 360(19):1960–1970

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Scholl UI, Choi M, Liu T, Ramaekers VT, Hausler MG, Grimmer J, Tobe SW, Farhi A, Nelson-Williams C, Lifton RP (2009) Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10. Proc Natl Acad Sci U S A 106(14):5842–5847

    Article  PubMed  PubMed Central  Google Scholar 

  78. Janer A, van Karnebeek CD, Sasarman F, Antonicka H, Al Ghamdi M, Shyr C, Dunbar M, Stockler-Ispiroglu S, Ross CJ, Vallance H, Dionne J, Wasserman WW, Shoubridge EA (2015) RMND1 deficiency associated with neonatal lactic acidosis, infantile onset renal failure, deafness, and multiorgan involvement. Eur J Hum Genet 23(10):1301–1307

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Ravn K, Neland M, Wibrand F, Duno M, Ostergaard E (2016) Hearing impairment and renal failure associated with RMND1 mutations. Am J Med Genet A 170A(1):142–147

    Article  PubMed  CAS  Google Scholar 

  80. Karet FE, Finberg KE, Nelson RD, Nayir A, Mocan H, Sanjad SA, Rodriguez-Soriano J, Santos F, Cremers CW, Di Pietro A, Hoffbrand BI, Winiarski J, Bakkaloglu A, Ozen S, Dusunsel R, Goodyer P, Hulton SA, Wu DK, Skvorak AB, Morton CC, Cunningham MJ, Jha V, Lifton RP (1999) Mutations in the gene encoding B1 subunit of H+−ATPase cause renal tubular acidosis with sensorineural deafness. Nat Genet 21(1):84–90

    Article  PubMed  CAS  Google Scholar 

  81. Smith AN, Skaug J, Choate KA, Nayir A, Bakkaloglu A, Ozen S, Hulton SA, Sanjad SA, Al-Sabban EA, Lifton RP, Scherer SW, Karet FE (2000) Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing. Nat Genet 26(1):71–75

    Article  PubMed  CAS  Google Scholar 

  82. Stover EH, Borthwick KJ, Bavalia C, Eady N, Fritz DM, Rungroj N, Giersch AB, Morton CC, Axon PR, Akil I, Al-Sabban EA, Baguley DM, Bianca S, Bakkaloglu A, Bircan Z, Chauveau D, Clermont MJ, Guala A, Hulton SA, Kroes H, Li Volti G, Mir S, Mocan H, Nayir A, Ozen S, Rodriguez Soriano J, Sanjad SA, Tasic V, Taylor CM, Topaloglu R, Smith AN, Karet FE (2002) Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. J Med Genet 39(11):796–803

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Vargas-Poussou R, Houillier P, Le Pottier N, Strompf L, Loirat C, Baudouin V, Macher MA, Dechaux M, Ulinski T, Nobili F, Eckart P, Novo R, Cailliez M, Salomon R, Nivet H, Cochat P, Tack I, Fargeot A, Bouissou F, Kesler GR, Lorotte S, Godefroid N, Layet V, Morin G, Jeunemaitre X, Blanchard A (2006) Genetic investigation of autosomal recessive distal renal tubular acidosis: evidence for early sensorineural hearing loss associated with mutations in the ATP6V0A4 gene. J Am Soc Nephrol 17(5):1437–1443

    Article  PubMed  CAS  Google Scholar 

  84. Wall SM, Lazo-Fernandez Y (2015) The role of pendrin in renal physiology. Annu Rev Physiol 77:363–378

    Article  PubMed  CAS  Google Scholar 

  85. Pendred V (1896) Deaf-mutism and goitre. Lancet 148(3808):532

    Article  Google Scholar 

  86. Pela I, Bigozzi M, Bianchi B (2008) Profound hypokalemia and hypochloremic metabolic alkalosis during thiazide therapy in a child with Pendred syndrome. Clin Nephrol 69(6):450–453

    Article  PubMed  CAS  Google Scholar 

  87. Soleimani M, Barone S, Xu J, Shull GE, Siddiqui F, Zahedi K, Amlal H (2012) Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure. Proc Natl Acad Sci U S A 109(33):13368–13373

    Article  PubMed  PubMed Central  Google Scholar 

  88. Yang T, Vidarsson H, Rodrigo-Blomqvist S, Rosengren SS, Enerback S, Smith RJ (2007) Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4). Am J Hum Genet 80(6):1055–1063

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

We would like to thank Alexander Cramer for the illustrations in Figs. 1 and 2.

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Authors and Affiliations

  1. Department of Nephrology, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK

    Paul J. Phelan

  2. Department of Pediatrics, Division of Nephrology, University of Minnesota Masonic Children’s Hospital, Minneapolis, MN, USA

    Michelle N. Rheault

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  1. Paul J. Phelan
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Correspondence to Michelle N. Rheault.

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1. c; 2. a; 3. d; 4. e; 5. a

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Phelan, P.J., Rheault, M.N. Hearing loss and renal syndromes. Pediatr Nephrol 33, 1671–1683 (2018). https://doi.org/10.1007/s00467-017-3835-9

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