branchio oto renal syndrome


Summary: An autosomal dominant disorder manifested by various combinations of preauricular pits, branchial fistulae or cysts, lacrimal duct stenosis, hearing loss, structural defects of the outer, middle, or inner ear, and renal dysplasia. Associated defects include asthenic habitus, long narrow facies, constricted palate, deep overbite, and myopia. Hearing loss may be due to Mondini type cochlear defect and stapes fixation. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)

Top Publications

  1. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, et al. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet. 1997;15:157-64 pubmed
    ..In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches. ..
  2. Zhang Y, Knosp B, Maconochie M, Friedman R, Smith R. A comparative study of Eya1 and Eya4 protein function and its implication in branchio-oto-renal syndrome and DFNA10. J Assoc Res Otolaryngol. 2004;5:295-304 pubmed
    ..These results are consistent with clinical data and implicate haploinsufficiency as the cause of BOR syndrome and DFNA10. ..
  3. Mutsuddi M, Chaffee B, Cassidy J, Silver S, Tootle T, Rebay I. 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. 2005;170:687-95 pubmed
  4. Kulkarni M, Deshmukh S, Kumar A, Kulkarni P. Branchio-oculo-facial syndrome. Indian J Pediatr. 2005;72:701-3 pubmed
    ..We report three members of one family, showing great variability in its phenotypic expression and review the recent literature. ..
  5. Verret D, Murray A, Hobar P. Branchio-oculo-facial syndrome with ectodermal parathyroid tissue. Otolaryngol Head Neck Surg. 2005;133:983-4 pubmed
  6. Stoetzel C, Riehm S, Bennouna Greene V, Pelletier V, Vigneron J, Leheup B, et al. Confirmation of TFAP2A gene involvement in branchio-oculo-facial syndrome (BOFS) and report of temporal bone anomalies. Am J Med Genet A. 2009;149A:2141-6 pubmed publisher
    ..Moreover, we present CT scan temporal bone anomalies in the familial cases, related to branchial arch defects, highlighting the importance of radiological investigations for differential diagnosis...
  7. Kapoor S, Kapur N. Branchio-oculo-facial syndrome with valvular pulmonic stenosis. Indian Pediatr. 2004;41:1180-1 pubmed
  8. Demirci H, Shields C, Shields J. New ophthalmic manifestations of branchio-oculo-facial syndrome. Am J Ophthalmol. 2005;139:362-4 pubmed
    ..In this case, the ophthalmic manifestations included lacrimal sac fistula, orbital dermoid cyst, iris pigment epithelial cyst, and combined hamartoma of the retina and retinal pigment epithelium. ..
  9. Ito T, Noguchi Y, Yashima T, Kitamura K. SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome. Laryngoscope. 2006;116:796-9 pubmed
    ..The objectives of this study were to identify SIX1 gene mutations in a patient with branchio-oto syndrome (BO) and to clarify the relationship between SIX1 mutation and enlargement of the vestibular aqueduct (EVA)...

More Information


  1. Rayapureddi J, Hegde R. Branchio-oto-renal syndrome associated mutations in Eyes Absent 1 result in loss of phosphatase activity. FEBS Lett. 2006;580:3853-9 pubmed
    ..Furthermore we demonstrate that the N-terminal domain attenuates the catalytic activity of Eya suggesting a mechanism of regulation. ..
  2. Buller C, Xu X, Marquis V, Schwanke R, Xu P. Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome. Hum Mol Genet. 2001;10:2775-81 pubmed
    ..However, four mutations are crucial for protein-protein interactions in both yeast and mammalian cells. Our results provide insights into the molecular mechanisms of organ defects detected in human syndromes. ..
  3. Kumar S, Deffenbacher K, Cremers C, Van Camp G, Kimberling W. Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing. Genet Test. 1997;1:243-51 pubmed
    ..These results provide the basis for molecular genetic testing that will help in the clinical evaluation and genetic counseling of members of BOR families. ..
  4. Milunsky J, Maher T, Zhao G, Roberts A, Stalker H, Zori R, et al. TFAP2A mutations result in branchio-oculo-facial syndrome. Am J Hum Genet. 2008;82:1171-7 pubmed publisher
    ..We conclude BOFS is caused by mutations involving TFAP2A. More patients need to be studied to determine possible genetic heterogeneity and to establish whether there are genotype-phenotype correlations. ..
  5. Su C, O Hagen S, Sullivan T. Ocular anomalies in the branchio-oculo-facial syndrome. Aust N Z J Ophthalmol. 1998;26:43-6 pubmed
    ..It has an autosomal dominant inheritance pattern. ..
  6. Bennaceur S, Buisson T, Bertolus C, Couly G. Branchio-oculo-facial syndrome with cleft lip and bilateral dermal thymus. Cleft Palate Craniofac J. 1998;35:454-9 pubmed
  7. Lin A, Semina E, Daack Hirsch S, Roeder E, Curry C, Rosenbaum K, et al. Exclusion of the branchio-oto-renal syndrome locus (EYA1) from patients with branchio-oculo-facial syndrome. Am J Med Genet. 2000;91:387-90 pubmed
    ..In light of these issues, we selected the BOR locus (EYA1) as a possible gene mutation for the BOF syndrome. In five BOF patients, there were no mutations detected in the EYA1 gene, suggesting that it is not allelic to the BOR syndrome. ..
  8. Rosa R, Zen P, Graziadio C, Paskulin G. Branchio-oculo-facial syndrome (BOFS) and congenital heart defects. Arq Bras Cardiol. 2009;92:e6-8, e33-5 pubmed
    ..This description strengthens the possibility of congenital heart defects being part of the spectrum of anomalies seen in BOFS. ..
  9. Azuma N, Hirakiyama A, Inoue T, Asaka A, Yamada M. Mutations of a human homologue of the Drosophila eyes absent gene (EYA1) detected in patients with congenital cataracts and ocular anterior segment anomalies. Hum Mol Genet. 2000;9:363-6 pubmed
    ..One of the patients had clinical features of BOR syndrome as well. This result implies that the human EYA1 gene is also involved in eye morphogenesis, and that a wide variety of clinical manifestations may be caused by EYA1 mutations. ..
  10. Xu P, Adams J, Peters H, Brown M, Heaney S, Maas R. Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet. 1999;23:113-7 pubmed
    ..In addition, our results suggest that an evolutionarily conserved Pax-Eya-Six regulatory hierarchy is used in mammalian ear and kidney development. ..
  11. Johnson K, Cook S, Erway L, Matthews A, Sanford L, Paradies N, et al. Inner ear and kidney anomalies caused by IAP insertion in an intron of the Eya1 gene in a mouse model of BOR syndrome. Hum Mol Genet. 1999;8:645-53 pubmed
    ..The new mouse mutation is designated Eya1(bor) to denote its similarity to human BOR syndrome, and will provide a valuable model for studying mutant gene expression and etiology. ..
  12. Pierides A, Athanasiou Y, Demetriou K, Koptides M, Deltas C. A family with the branchio-oto-renal syndrome: clinical and genetic correlations. Nephrol Dial Transplant. 2002;17:1014-8 pubmed
    ..The BOR syndrome should be included in the differential diagnosis of deafness and chronic renal failure in childhood and adolescence. ..
  13. El Darouti M, Marzouk S, Azzam O, Nada H, Sobhi R, El Nabarawi I. Branchio-oculo-facial syndrome with bilateral linear scars of the neck. Int J Dermatol. 2005;44:674-6 pubmed
    ..We believe that the latter lesions may represent the end stage of dermal thymus; a rare condition which has been reported so far in only four cases, two of which had branchio-oculo-facial syndrome. ..
  14. Ruf R, Xu P, Silvius D, Otto E, Beekmann F, Muerb U, et al. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci U S A. 2004;101:8090-5 pubmed
    ..Identification of SIX1 mutations as causing BOR/BO offers insights into the molecular basis of otic and renal developmental diseases in humans. ..
  15. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, et al. Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1. Hum Mol Genet. 1997;6:2247-55 pubmed
    ..To date, 14 mutations have been detected in BOR patients, all of which are different. However, all the mutations are located within or in the immediate vicinity of the eyaHR; the significance of this clustering is discussed. ..
  16. Tekin M, Sirmaci A, Yüksel Konuk B, Fitoz S, Sennaroglu L. A complex TFAP2A allele is associated with branchio-oculo-facial syndrome and inner ear malformation in a deaf child. Am J Med Genet A. 2009;149A:427-30 pubmed publisher
    ..Our report implies that the localization of mutations in TFAP2A might be responsible with the phenotypic findings in BOF syndrome. ..
  17. Ozturk O, Tokmak A, Demirci L, Silan F, Guclu E. Branchio-oculo-facial syndrome with the atresia of external ear. Int J Pediatr Otorhinolaryngol. 2005;69:1575-8 pubmed
    ..His mother had pseudocleft of the lip which led to the diagnosis. The importance of serial observations in patients with rare genetic disorders is emphasized...
  18. Hiroshi Furukawa -, Satoru Sasaki -, Eisuke Uchiyama -, Kunihiro Kawashima -, Yuhei Yamamoto -. Bilateral dermal thymus of neck in branchio-oculo-facial syndrome. J Plast Reconstr Aesthet Surg. 2006;59:1385-7 pubmed
    ..Ectopic thymus can be excised completely after careful evaluation of haematologic, immunologic status if normal thymic shadow cannot be identified on chest X-p. ..
  19. Hoskins B, Cramer C, Silvius D, Zou D, Raymond R, Orten D, et al. Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. Am J Hum Genet. 2007;80:800-4 pubmed
    ..We thereby identified heterozygous mutations in SIX5 as a novel cause of BOR. ..
  20. Orten D, Fischer S, Sorensen J, Radhakrishna U, Cremers C, Marres H, et al. Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR. Hum Mutat. 2008;29:537-44 pubmed publisher
    ..These results add considerably to the spectrum of EYA1 mutations associated with BOR and indicate that the BOR phenotype is an indication for molecular studies to diagnose EYA1-associated BOR. ..
  21. Skarzynski H, Podskarbi Fayette R. Treatment of otorhinolaryngological manifestations of three rare genetic syndromes: Branchio-Oculo-Facial (BOF), Ectrodactyly Ectodermal dysplasia Clefting (EEC) and focal dermal hypoplasia (Goltz syndrome). Int J Pediatr Otorhinolaryngol. 2009;73:143-51 pubmed publisher
    ..However, it is of crucial importance in such cases to focus on hearing improvement in order to reach and maintain hearing at the level of social communication. ..
  22. Lin A, Yuzuriha S, McLean S, Mulliken J. Lesser forms of cleft lip associated with the branchio-oculo-facial syndrome. J Craniofac Surg. 2009;20 Suppl 1:608-11 pubmed
    ..Another possible pathogenic explanation is that failure of labial closure occurs earlier than in a major cleft when the primitive cells of ectoderm and mesoderm retain the capacity to "heal" the defect. ..
  23. Senel E, Kocak H, Akbiyik F, Saylam G, Gulleroglu B, Senel S. From a branchial fistula to a branchiootorenal syndrome: a case report and review of the literature. J Pediatr Surg. 2009;44:623-5 pubmed publisher
    ..The aim of this report is to make pediatric surgeons aware of the BOR syndrome in patients presenting with branchial arch anomalies. ..
  24. Patrick A, Schiemann B, Yang K, Zhao R, Ford H. Biochemical and functional characterization of six SIX1 Branchio-oto-renal syndrome mutations. J Biol Chem. 2009;284:20781-90 pubmed publisher
  25. Kwon M, Boo S, Kim H, Cho Y, Chung W, Hong S. A novel splice site mutation in the EYA1 gene in a Korean family with branchio-oto (BO) syndrome. Acta Otolaryngol. 2009;129:688-93 pubmed publisher
    ..To the best of our knowledge, this is the first report of a splice site mutation in a family with BO syndrome without renal involvement, further extending the phenotypic-genotypic heterogeneity of BOR/BO syndrome. ..
  26. Chang E, Menezes M, Meyer N, Cucci R, Vervoort V, Schwartz C, et al. Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences. Hum Mutat. 2004;23:582-9 pubmed
    ..We conclude that genetic testing of EYA1 should include analysis of the coding sequence and a screen for complex rearrangements. ..
  27. David J, Shanbag P. Branchio-oto-renal syndrome presenting with syndrome of hyporeninemic hypoaldosteronism. Saudi J Kidney Dis Transpl. 2017;28:1165-1168 pubmed publisher
    ..The child also had mental retardation and spastic diplegia which have hitherto not been described in BOR syndrome...
  28. Hone S, Smith R. Genetics of hearing impairment. Semin Neonatol. 2001;6:531-41 pubmed
    ..The implications of this finding for screening and genetic counseling are discussed. ..
  29. Kalatzis V, Sahly I, El Amraoui A, Petit C. Eya1 expression in the developing ear and kidney: towards the understanding of the pathogenesis of Branchio-Oto-Renal (BOR) syndrome. Dev Dyn. 1998;213:486-99 pubmed
  30. D Eredità R, Marchi M. Ossicular chain dystopia and dilation of vestibules in branchio-oto-renal syndrome: a new phenotypic association?. Otolaryngol Head Neck Surg. 2002;126:206-8 pubmed
  31. Uno T, Sawada M, Kurotaki T, Shinomiya N. EYA1 gene nonsense mutation in a Japanese family with branchio-oto-renal syndrome. Pediatr Int. 2004;46:615-7 pubmed
  32. Niu H, Li X, Makmura L, Friedman R. Mapping of genetic modifiers of Eya1 ( bor/bor ) in CAST/EiJ and BALB/cJ that suppress cochlear aplasia and associated deafness. Mamm Genome. 2008;19:634-9 pubmed publisher
    ..The identification of these additional modifier alleles could provide crucial clues for evaluating the candidate genes. ..
  33. Scheinfeld N, Silverberg N, Weinberg J, Nozad V. The preauricular sinus: a review of its clinical presentation, treatment, and associations. Pediatr Dermatol. 2004;21:191-6 pubmed
    ..Recurrence rates after surgery range from 9% to 42%. Meticulous excision by an experienced head and neck surgeon minimizes the risk of recurrence. ..
  34. Sikora P, Zajaczkowska M, Katska E, Niedzielska G. [A nineteen year observation of a boy with branchio-oto-renal syndrome and chronic renal failure]. Pol Merkur Lekarski. 2001;10:291-3 pubmed
  35. Rickard S, Boxer M, Trompeter R, Bitner Glindzicz M. Importance of clinical evaluation and molecular testing in the branchio-oto-renal (BOR) syndrome and overlapping phenotypes. J Med Genet. 2000;37:623-7 pubmed
  36. Bellini C, Piaggio G, Massocco D, Perfumo F, Bertini -, Gusmano R, et al. Branchio-Oto-renal syndrome: a report on nine family groups. Am J Kidney Dis. 2001;37:505-9 pubmed
    ..After BOR syndrome has been diagnosed in a patient, all family members should be examined for the presence of the syndrome, even if there are only minimal stigmata of the disease. ..
  37. Reiber J, Sznajer Y, Posteguillo E, Müller D, Lyonnet S, Baumann C, et al. Additional clinical and molecular analyses of TFAP2A in patients with the branchio-oculo-facial syndrome. Am J Med Genet A. 2010;152A:994-9 pubmed publisher
    ..Our study represents the second group of BOFS patients with molecular confirmation, expanding the phenotype and spectrum of mutations and limiting it to a restricted part of the gene. ..
  38. Unzaki A, Morisada N, Nozu K, Ye M, Ito S, Matsunaga T, et al. Clinically diverse phenotypes and genotypes of patients with branchio-oto-renal syndrome. J Hum Genet. 2018;63:647-656 pubmed publisher
    ..Even within the same family, renal phenotypes often varied substantially. In addition to direct sequencing, MLPA and NGS were useful for the genetic analysis of BOR patients. ..
  39. Fukuda S, Kuroda T, Chida E, Shimizu R, Usami S, Koda E, et al. A family affected by branchio-oto syndrome with EYA1 mutations. Auris Nasus Larynx. 2001;28 Suppl:S7-11 pubmed
    ..The present report adds further examples to support the usefulness of molecular genetic testing for the diagnosis of patients with BO syndrome. ..
  40. Propst E, Blaser S, Gordon K, Harrison R, Papsin B. Temporal bone findings on computed tomography imaging in branchio-oto-renal syndrome. Laryngoscope. 2005;115:1855-62 pubmed
    ..We ask if it is possible for the untrained observer to use a battery of CT observations as a tool in the overall evaluation of the BOR phenotype...
  41. Just W, Trautmann T, Baumstark A, Müller D. Exclusion of the SALL1 gene as a cause of branchio-oculo-facial syndrome. Am J Med Genet A. 2003;117A:196-8 pubmed
  42. Drut R, Galliani C. Thymic tissue in the skin: a clue to the diagnosis of the branchio-oculo-facial syndrome: report of two cases. Int J Surg Pathol. 2003;11:25-8 pubmed
    ..Thymic tissue at the skin appears to be unique for BOF syndrome and in a given case may provide the clue for the accurate diagnosis of the malformation complex. ..
  43. Vachharajani A, Uong E. The role of polysomnography in the diagnosis of a neuromuscular disorder. J Clin Sleep Med. 2005;1:398-9 pubmed
  44. Kochhar A, Fischer S, Kimberling W, Smith R. Branchio-oto-renal syndrome. Am J Med Genet A. 2007;143A:1671-8 pubmed
    ..Further evaluation of SIX1 and its related target genes may provide a better understanding of the pathophysiology of BOR syndrome and offer greater clues to the disease mechanisms. ..
  45. Trummer T, Muller D, Schulze A, Vogel W, Just W. Branchio-oculo-facial syndrome and branchio-otic/branchio-oto-renal syndromes are distinct entities. J Med Genet. 2002;39:71-3 pubmed
  46. Ceruti S, Stinckens C, Cremers C, Casselman J. Temporal bone anomalies in the branchio-oto-renal syndrome: detailed computed tomographic and magnetic resonance imaging findings. Otol Neurotol. 2002;23:200-7 pubmed
    ..Other malformations of the middle ear included a reduced middle ear cavity and malformations of the ossicular chain. ..
  47. Li Y, Manaligod J, Weeks D. EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis. Biol Cell. 2010;102:277-92 pubmed publisher
    ..These studies lend support to the hypothesis that dominant-negative effects of EYA1 mutations may have a role in the pathogenesis of BOR. ..
  48. Nie X, Sun J, Gordon R, Cai C, Xu P. SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation. Development. 2010;137:755-65 pubmed publisher
    ..These findings uncover an essential role for Six1 in establishing a functionally normal ureter and provide new insights into the molecular basis of urinary tract malformations in BOR patients. ..
  49. Au P, Chernos J, Thomas M. Review of the recurrent 8q13.2q13.3 branchio-oto-renal related microdeletion, and report of an additional case with associated distal arthrogryposis. Am J Med Genet A. 2016;170:2984-2987 pubmed publisher
    ..3. In addition to BOR related features, our patient presented with distal arthrogryposis that was detected prenatally, a phenotype that has not previously been described in patients with this deletion. © 2016 Wiley Periodicals, Inc. ..
  50. Henriksen A, Tumer Z, Tommerup N, Tranebjaerg L, Larsen L. Identification of a novel EYA1 splice-site mutation in a Danish branchio-oto-renal syndrome family. Genet Test. 2004;8:404-6 pubmed
    ..We conclude that this mutation is causing BOR in the family, most likely as a result of haploinsufficiency or an abnormal protein product caused by aberrant splicing of EYA1 mRNA. ..
  51. Kemperman M, Stinckens C, Kumar S, Huygen P, Joosten F, Cremers C. Progressive fluctuant hearing loss, enlarged vestibular aqueduct, and cochlear hypoplasia in branchio-oto-renal syndrome. Otol Neurotol. 2001;22:637-43 pubmed
    ..To study the results of petrosal bone imaging and audiometric long-term follow-up of two patients with branchio-oto-renal (BOR) syndrome and relate them to the clinical features, including caloric responses...
  52. Garg A, Wadhera R, Gulati S, Kumar A. Branchio-oto-renal syndrome. J Assoc Physicians India. 2008;56:904-5 pubmed
    ..Authors are reporting a 19 year male patient, who presented with profound deafness & low set "lop-ear" with right sided preauricular pit. USG abdomen revealed agenesis of the left kidney...
  53. Homer J, Roberts A, Wengraf C. In-the-ear hearing aids within auricular prostheses. J Laryngol Otol. 2001;115:998-1000 pubmed
    ..The prostheses themselves were successfully secured using a prosthetic contact adhesive we have developed that offers excellent retention, little if any skin reaction, and high patient acceptability. ..