January 17, 2018
Years published: 1992, 1994, 2004, 2007, 2018
NORD gratefully acknowledges Caroline Kim, NORD Editorial Intern from the Keck Graduate Institute and Richard JH Smith, MD, Sterba Hearing Research Professor and Vice Chair – Department of Otolaryngology, Director – Molecular Otolaryngology and Renal Research Laboratories, Professor of Otolaryngology, Molecular Physiology & Biophysics, Pediatrics, and Internal Medicine (Division of Nephrology), for assistance in the preparation of this report.
Branchiootorenal spectrum disorders are inherited as autosomal dominant genetic conditions that can vary greatly from one person to another, even in members of the same family.
Branchiootorenal (BOR) syndrome is characterized by pits or ear tags in front of the outer ear (preauricular pits), abnormal passages from the throat to the outside surface of the neck (branchial fistulas), branchial cysts, malformations of the outer, middle and inner ear, hearing loss and kidney (renal) abnormalities.
Individuals with branchiootic (BOS) syndrome have the ear and hearing abnormalities but kidneys are not affected.
Most people with BOR/BOS syndrome have some type of hearing loss. The hearing loss may be due to nerve damage (sensory), blockage of sound waves (conductive), or both. The degree of hearing loss varies from mild to profound, and can differ between the two ears. The deafness can be stable or progressive. Other abnormalities related to the ear that may be present include pits or outgrowths of cartilage (tags) in front of the outer ear; a cupped or small outer ear; and/or a narrow or upward slanted outer ear canal.
An abnormal passage from the throat to the outside surface of the neck (branchial fistula), and/or an opening on the side of the neck, or a mass that can be felt under the muscles on the side of the neck is often present.
The kidney abnormalities associated with BOR syndrome range from mild to very severe. In milder cases, the kidney may be unusually shaped. In more severe cases, there may be duplication of the collecting system of the kidneys and/or absence or failure of one or both of the kidneys to form.
Other abnormalities that have been found in association with BOR syndrome are narrowing of the tear duct in the eyes interfering with the normal flow of tears; a long narrow face; cleft palate; paralysis of certain muscles in the face; and/or a deep overbite.
BOR/BOS syndrome is caused by mutations in the EYA1(BOR1, BOS2), SIX5 (BOR2), and SIX1 (BOR3, BOS3) genes.
BOR/BOS syndrome is inherited as an autosomal dominant disorder. Dominant genetic disorders occur when one copy of a gene is abnormal and this abnormal copy results in the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
BOR/BOS syndrome affects males and females in equal numbers. It is estimated that 1 in 40,000 people have this disorder. BOR/BOS syndrome is found in approximately 2 to 3 percent of children with profound deafness.
The diagnosis of BOR/BOS syndrome is made when at least two of five features (branchial defects, hearing loss, preauricular pits, abnormalities of the part of the ear that projects from the head (pinna), and renal malformations) are present in an individual with two or more affected family members, or three features are present in an individual with no affected family members.
Evaluation of hearing function (audiologic assessment), and imaging (CT or computerized tomography) of the temporal bone to identify the middle and inner ear defects, should be performed. Renal abnormality is investigated by urinalysis, renal function tests, and imaging studies such as renal ultrasonography and CT.
Molecular genetic testing for mutations in the EYA1(BOR1, BOS2), SIX5 (BOR2), and SIX1 (BOR3, BOS3) genes is available to confirm a clinical diagnosis of BOR/BOS syndrome.
EYA1 mutations are be found in about 40% of people with BOR/BOS syndrome. A SIX1 mutation is estimated to be found in 4% of people with BOR/BOS syndrome and a SIX5 mutation is present in about 5% of people with BOR/BOS syndrome.
The child with hearing impairment should undergo appropriate rehabilitation measures with annual hearing testing (audiometry). Medical attention should be sought promptly for any episode of inflammation of the middle ear (otitis media).
Patients with BOR/BOS syndrome may benefit from hearing aids. When structural defects of the ear are present, surgery may be beneficial.
Branchial cleft deformities have the potential to become easily infected and may require surgical treatment such as excision of the branchial cleft cyst or fistulae. Antibiotics can be given if the cyst or sinuses are infected. Also, a physician specializing in kidney problems (nephrologist) should closely monitor any renal impairment. Surgical repair may be undertaken for correctable defects. Severe kidney problems may warrant dialysis or kidney transplantation.
Semiannual examination for hearing impairment is recommended to assess stability of hearing loss. Semiannual examination for renal function is recommended to prevent progression of worsening of the kidneys.
Genetic counseling is recommended for patients and their families. Other treatment is symptomatic and supportive.
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Branchiootorenal syndrome. Genetic and Rare Diseases Information Center. Last updated: 2/28/2011. Available at: https://rarediseases.info.nih.gov/diseases/10147/branchiootorenal-syndrome. Accessed January 17, 2018.
Smith RJH. Branchiootorenal Spectrum Disorders. 1999 Mar 19 [Updated 2015 Oct 22]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1380/ Accessed January 17, 2018.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Branchiootorenal Syndrome. Entry Number; 113650: Last Edit Date;12/04/2014. Available at: https://www.omim.org/entry/113650?search=113650&highlight=113650 Accessed January 17, 2018.
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