Branchio-oto-renal syndrome explained

Branchio-oto-renal syndrome
Synonyms:BOR syndrome, Branchiootorenal syndrome
Symptoms:Ear abnormalities
Causes:Mutations in genes, EYA1, SIX1, and SIX5
Diagnosis:Laboratory test results, Physical exam
Treatment:Branchial fistula may need surgery

Branchio-oto-renal syndrome (BOR)[1] [2] is an autosomal dominant genetic disorder involving the kidneys, ears, and neck. It is also known as Melnick-Fraser syndrome.[3] [4]

Signs and symptoms

The signs and symptoms of branchio-oto-renal syndrome are consistent with underdeveloped (hypoplastic) or absent kidneys with resultant chronic kidney disease or kidney failure. Ear anomalies include extra openings in front of the ears, extra pieces of skin in front of the ears (preauricular tags), or further malformation or absence of the outer ear (pinna). Malformation or absence of the middle ear is also possible, individuals can have mild to profound hearing loss. People with BOR may also have cysts or fistulae along the sides of their neck.[5] In some individuals and families, renal features are completely absent. The disease may then be termed "branchio-oto syndrome" (BO syndrome).[6] [7]

Cause

The cause of branchio-oto-renal syndrome are mutations in genes, EYA1, SIX1, and SIX5 (approximately 40 percent of those born with this condition have a mutation in the EYA1 gene).[5] [8] Many different abnormalities in these genes have been identified.[9]

Mechanism

The genetics of branchio-oto-renal syndrome indicate it is inherited in an autosomal dominant manner with variable clinical manifestations affecting branchial, renal, and auditory development. Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. The varying clinical expression of the disease between different families suggests that multiple loci may be involved. In 1992, using genetic linkage studies, the BOR gene was identified on chromosome 8,[10] Subsequently, another locus on human chromosome 14 was identified, and several mutations were reported in genes EYA1, SIX1,[11] and SIX5.[12] SINX1 is involved in many facets of embryonic development and is important in the normal formation of many organs and tissues, including the ears, and kidneys before birth.[13]

Diagnosis

Diagnosis of BO syndrome or BOR syndrome is clinical, i.e. based on observing an appropriate combination of symptoms.[6] Only about half of patients have a detectable genetic abnormality, mostly in the EYA1 gene, SIX1 gene or the SIX5 gene.[6]

Treatment

The treatment of branchio-oto-renal syndrome is done per each affected area (or organ). For example, a person with hearing problems should have appropriate supports and prompt attention for any inflammation of the ear.[6] [14]

A specialist should observe any kidney problems. Surgical repair may be needed depending on the degree of a defect or problem, whether a transplant or dialysis is needed.[15]

Epidemiology

The epidemiology of branchio-oto-renal syndrome has it with a prevalence of 1/40,000 in Western countries. A 2014 review found 250 such cases in the country of Japan.[16]

See also

Further reading

Notes and References

  1. Book: Genetic Hearing Loss . Kumar S . Willems PJ . Marcel Dekker Inc . 2004 . New York . Branchio-oto-renal Syndrome . 10.1201/9780203913062 . 9780203913062 . https://www.taylorfrancis.com/chapters/edit/10.1201/9780203913062-15/branchio-oto-renal-syndrome-shrawan-kumar . 2022-11-13 . 2022-11-13 . https://web.archive.org/web/20221113032729/https://www.taylorfrancis.com/chapters/edit/10.1201/9780203913062-15/branchio-oto-renal-syndrome-shrawan-kumar . live .
  2. Kumar S, Deffenbacher K, Cremers CW, Van Camp G, Kimberling WJ . Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing . Genetic Testing . 1 . 4 . 243–251 . 1997 . 10464653 . 10.1089/gte.1997.1.243 .
  3. Web site: Branchiootorenal syndrome. Genetics Home Reference . U.S. National Library of Medicine . 2015-11-23. 2015-11-29. 2016-02-29. https://web.archive.org/web/20160229094635/http://ghr.nlm.nih.gov/condition/branchiootorenal-syndrome. dead.
  4. Web site: Branchiootorenal syndrome Disease Overview . Genetic and Rare Diseases Information Center (GARD) – an NCATS Program . 2015-11-29 . 2016-07-27 . https://web.archive.org/web/20160727230535/https://rarediseases.info.nih.gov/gard/10147/disease/resources/1 . dead .
  5. Web site: Branchio Oto Renal Syndrome . NORD (National Organization for Rare Disorders) . 2015-11-29 . en-US . 2020-09-26 . https://web.archive.org/web/20200926120103/https://rarediseases.org/rare-diseases/branchio-oto-renal-syndrome/ . live .
  6. Book: Branchiootorenal Spectrum Disorders. https://www.ncbi.nlm.nih.gov/books/NBK1380/. University of Washington, Seattle. 1993-01-01. Seattle (WA). 20301554. Smith RJ. Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Fong C, Mefford HC. 6. Branchiootorenal Spectrum Disorder. 2017-08-30. 2021-03-09. https://web.archive.org/web/20210309180646/https://www.ncbi.nlm.nih.gov/books/NBK1380/. live. |updated, 2015|
  7. Kumar S, Marres HA, Cremers CW, Kimberling WJ . Autosomal-dominant branchio-otic (BO) syndrome is not allelic to the branchio-oto-renal (BOR) gene at 8q13 . American Journal of Medical Genetics . 76 . 5 . 395–401 . April 1998 . 9556298 . 10.1002/(sici)1096-8628(19980413)76:5<395::aid-ajmg6>3.0.co;2-m .
  8. Book: Kidney Development, Disease, Repair and Regeneration. Academic Press. 2015-08-06. 269. 9780128004388. en. Little MH .
  9. Smith RJ (1993). Adam MP, Everman DB, Mirzaa GM, Pagon RA (eds.). Branchiootorenal Spectrum Disorder. Seattle (WA): University of Washington, Seattle. PMID 20301554
  10. Kumar S, Kimberling WJ, Kenyon JB, Smith RJ, Marres HA, Cremers CW . Autosomal dominant branchio-oto-renal syndrome--localization of a disease gene to chromosome 8q by linkage in a Dutch family . Human Molecular Genetics . 1 . 7 . 491–495 . October 1992 . 1307249 . 10.1093/hmg/1.7.491 .
  11. Ruf RG, Xu PX, Silvius D, Otto EA, Beekmann F, Muerb UT, Kumar S, Neuhaus TJ, Kemper MJ, Raymond RM, Brophy PD, Berkman J, Gattas M, Hyland V, Ruf EM, Schwartz C, Chang EH, Smith RJ, Stratakis CA, Weil D, Petit C, Hildebrandt F . 6 . SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes . Proceedings of the National Academy of Sciences of the United States of America . 101 . 21 . 8090–8095 . May 2004 . 15141091 . 419562 . 10.1073/pnas.0308475101 . 2004PNAS..101.8090R . free .
  12. Krug P, Morinière V, Marlin S, Koubi V, Gabriel HD, Colin E, Bonneau D, Salomon R, Antignac C, Heidet L . 6 . Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenic role of SIX5 mutations . Human Mutation . 32 . 2 . 183–190 . February 2011 . 21280147 . 10.1002/humu.21402 . 25826641 . 2022-11-13 . 2022-11-13 . https://web.archive.org/web/20221113090052/https://hal.archives-ouvertes.fr/hal-00612007/file/PEER_stage2_10.1002%252Fhumu.21402.pdf . live .
  13. Mehdizadeh T, Majumdar HD, Ahsan S, Tavares AL, Moody SA . Mutations in SIX1 Associated with Branchio-oto-Renal Syndrome (BOR) Differentially Affect Otic Expression of Putative Target Genes . Journal of Developmental Biology . 9 . 3 . 25 . June 2021 . 34208995 . 8293042 . 10.3390/jdb9030025 . free .
  14. Book: Cochlear Implants: Principles & Practices. Lippincott Williams & Wilkins. 2009-01-01. 53. 9780781777490. en. Niparko JK. John Niparko. 2020-11-25. 2023-01-12. https://web.archive.org/web/20230112052613/https://books.google.com/books?id=VUisHOM--UkC&q=Branchio-oto-renal%2520syndrome&pg=PA53. live.
  15. Izzedine H, Tankere F, Launay-Vacher V, Deray G . Ear and kidney syndromes: molecular versus clinical approach . Kidney International . 65 . 2 . 369–385 . February 2004 . 14717907 . 10.1111/j.1523-1755.2004.00390.x . free .
  16. Morisada N, Nozu K, Iijima K . Branchio-oto-renal syndrome: comprehensive review based on nationwide surveillance in Japan . Pediatrics International . 56 . 3 . 309–314 . June 2014 . 24730701 . 10.1111/ped.12357 . 40930806 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Branchio-oto-renal syndrome".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.