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Branchiootorenal/Branchiootic Syndrome

Last updated Sept. 23, 2021

Approved by: Krish Tangella MD, MBA, FCAP

Branchiootorenal/Branchiootic Syndrome (BOR/BO Syndrome) is a congenital genetic disorder that falls under the category of Branchiootorenal Spectrum Disorders.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Branchiootic Syndrome (BOS)
  • Branchio-Oto-Renal Syndrome (BOR Syndrome)
  • Melnick-Fraser Syndrome

What is Branchiootorenal/Branchiootic Syndrome? (Definition/Background Information)

  • Branchiootorenal/Branchiootic Syndrome (BOR/BO Syndrome) is a congenital genetic disorder that falls under the category of Branchiootorenal Spectrum Disorders
  • The Branchiootorenal Syndrome is named based on the tissues and organs affected. “Branchio” refers to the second branchial arch, which gives rise to the front and sides of the neck during fetal development; “oto” refers to the ears; and “renal” refers to the kidneys. When the kidneys are not involved, the syndrome is termed Branchiootic Syndrome
  • In about 90% of the affected individuals the inherited form of Branchiootorenal/Branchiootic Syndrome is observed, implying that a family history of the condition is a major risk factor for developing the same
  • Mutations in the EYA1, SIX1, and SIX5 genes are associated with development of Branchiootorenal/Branchiootic Syndrome. These 3 genes code for proteins that interact with one another to bring about normal embryonic development
  • A mutation in any one of the aforementioned genes can lead to formation of aberrant protein, which does not allow for normal protein-protein interactions to occur
  • Some of the symptoms of Branchiootorenal/Branchiootic Syndrome can involve the neck, ear and kidneys. Lumps, masses, pits, and holes may be found in and on the neck and other adjoining regions
  • Middle ear and inner ear abnormalities associated with Branchiootorenal/Branchiootic Syndrome can lead to partial or complete deafness. Furthermore, there can be structural and functional abnormalities in the kidneys as a result of the condition
  • A diagnosis of Branchiootorenal/Branchiootic Syndrome can be made prenatally through fetal ultrasound and genetic testing of the fetal cells. A diagnosis after birth may require a physical examination, evaluation of family history, and assessment for characteristic symptoms
  • There is presently no cure for Branchiootorenal/Branchiootic Syndrome; however, the individual symptoms may be treated in order to offer some measure of comfort to the affected individuals
  • The cysts and holes (fistulae) of the neck may be surgically corrected. Ear abnormalities can be surgically improved along with hearing aids and special education for the hearing impaired. Further medication and surgical procedures may be required to treat the kidney issues
  • Life-long monitoring of the symptoms may be required in individuals with the disorder. Both the life-expectancy and intelligence in affected individuals are reported to be normal and the prognosis of Branchiootorenal/Branchiootic Syndrome is typically good

Who gets Branchiootorenal/Branchiootic Syndrome? (Age and Sex Distribution)

  • Branchiootorenal/Branchiootic Syndrome is reported to affect approximately 1 in 40,000 individuals
  • Both male and female genders can develop the disorder
  • The condition can affect any individual, regardless of race, ethnicity, or geographic location

What are the Risk Factors for Branchiootorenal/Branchiootic Syndrome? (Predisposing Factors)

  • Having a family history of Branchiootorenal/Branchiootic Syndrome is the single biggest risk factor for developing this condition
  • 2-3% of children with serious deafness are known to be affected by the BOR/BO Syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Branchiootorenal/Branchiootic Syndrome? (Etiology)

  • Branchiootorenal/Branchiootic Syndrome is reported to be caused by mutations in the EYA1, SIX1, and SIX5 genes
    • EYA1 mutations are seen in about 40% of those affected with BOR/BO Syndrome
    • Mutation(s) in the SIX1 gene accounts for a small proportion of the affected individuals
    • SIX5 mutations have been found in a small number of those with the syndrome. However, these individuals have later been found to have EYA1 mutations as well. This led scientists to believe that EYA1 mutations may be the major causative factor for BOR/BO Syndrome
    • These 3 genes code for proteins, which interact with each other to bring about normal development of an embryo. Mutations in these genes code for abnormal proteins that are incapable of binding other proteins in order to allow an embryo to develop normally
    • Such developmental abnormalities particularly seem to affect the tissues of the neck, and the formation of the ears and kidneys. This causes the symptoms observed with this syndrome
  • In approximately 90% of cases, the disorder is inherited as an autosomal dominant trait. In this type of inheritance, only a single copy of the defective gene is sufficient to cause disorder
  • In some of the remaining cases the disease is not inherited, but occurs as a result of spontaneous mutation(s) in one of the causative genes. Such individuals do not have a family history of the condition
  • In some individuals, no mutation(s) in the EYA1, SIX1, or SIX5 genes are observed. The exact cause of development of the syndrome in such cases remains unknown

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Branchiootorenal/Branchiootic Syndrome?

Branchio-Oto-Renal Syndrome affects the neck, ears, and kidneys, while Branchio-Otic Syndrome affects only the neck and ears. The major signs and symptoms of Branchiootorenal/Branchiootic Syndrome include:

  • Neck-related:
    • Branchial cysts: The presence of a mass/lump formation on one or both sides of the neck. The lump can also occur under the collarbone. It is also known as the branchial cleft remnant
    • Branchial fistula: The presence of an opening (hole or pits) in the neck, which might discharge mucus. The fistulae can cause tubular connections between the neck and the mouth, opening into the tonsils
    • Infection of the fistulae
    • Abscess formation in the fistulae
  • Ear-related:
    • Inner ear malformations
    • Middle ear abnormalities
    • Holes/pits in the skin of the ear
    • Extra skin in the ears
    • Hearing difficulties and deafness
  • Kidney-related: (in Branchio-Oto-Renal Syndrome)
    • Structural defects in one or both the kidneys
    • Compromised kidney function
    • Vesicoureteral reflux; the backflow of urine into the kidneys
    • Renal failure
    • End-stage renal disease
  • Palate (roof of mouth) and facial abnormalities, in some individuals

The signs and symptoms may vary in type and severity among the affected individuals, even if they are members of the same family.

How is Branchiootorenal/Branchiootic Syndrome Diagnosed?

The diagnosis of Branchiootorenal/Branchiootic Syndrome is undertaken through the following tests and procedures:

  • Prenatal diagnosis of BOR/BO Syndrome:
    • Ultrasound imaging studies
    • Genetic testing of fetal cells, when there is a family history of the condition
  • Diagnosis of BOR/BO Syndrome after birth:
    • Physical examination
    • An evaluation of family history
    • Hearing tests
    • Computed tomography (CT) imaging studies of neck abnormalities
    • Ultrasound scan of kidneys
    • CT scan of kidneys
    • Intravenous pyelography (excretory urography), which is an imaging test to check for blood in urine, kidney stones, bladder stones, or other abnormalities (such as cancer)
    • Urine test to check for kidney function (creatinine test, blood urea nitrogen or BUN test)
    • Genetic testing for confirmation of the syndrome

Diagnostic criteria:

  • In order to be diagnosed with Branchiootorenal/Branchiootic Syndrome, individuals with a family history of the condition need to have at least one major symptom
  • On the other hand, those with no family history of the syndrome need to have at least 3 of the major symptoms, or 2 each of the major and minor symptoms, to be diagnosed with the condition

The major and minor symptoms (or criteria) are given below:

  • Major symptoms:
    • Cysts or pit/hole in neck
    • Holes in the ear
    • Inner or middle ear malformations
    • Deafness
    • Abnormalities in kidney structure and/or function
  • Minor symptoms:
    • Outer ear abnormalities
    • Middle ear abnormalities
    • Inner ear abnormalities
    • Extra skin in the ears
    • Facial abnormalities

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Branchiootorenal/Branchiootic Syndrome?

The potential complications of Branchiootorenal/Branchiootic Syndrome may include the following:

  • Complete hearing loss
  • Backflow of urine into the kidneys, which can lead to progressive kidney failure
  • End-stage renal disease

How is Branchiootorenal/Branchiootic Syndrome Treated?

The treatment for Branchiootorenal/Branchiootic Syndrome typically addresses individual symptoms, since no cure exists for the disorder.

  • Neck-related symptoms: Surgical excision of cysts and fistulae
  • Ear-related symptoms:
    • Aural habilitation in young children who have not developed language skills, in order to improve their communication skills
    • Use of hearing aids
    • Canaloplasty, which is a surgery to widen the auditory canal
    • Special education for the hearing impaired
  • Kidneys-related symptoms:
    • Medication for urine backflow into the kidneys
    • Surgery to treat structural abnormalities, as well as for vesicoureteral reflux
    • Dialysis in case of renal failure
    • Kidney transplantation for end-stage renal disease

How can Branchiootorenal/Branchiootic Syndrome be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Branchiootorenal/Branchiootic Syndrome, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Branchiootorenal/branchiootic syndrome
  • Regular medical screening at periodic intervals with tests, and physical examinations are strongly recommended

Individuals with the Branchio-Oto-Renal Syndrome may need to avoid nephrotoxic medications, such as antibiotics and analgesics. Such medications may further damage the kidney function.

What is the Prognosis of Branchiootorenal/Branchiootic Syndrome? (Outcomes/Resolutions)

  • The prognosis for Branchiootorenal/Branchiootic Syndrome is reported to be good, with a vast majority of affected individuals having normal intelligence and life span. Nevertheless, life-long monitoring of symptoms is essential
  • The prognosis depends upon the severity of the signs and symptoms. Individuals with mild cases of BOR/BO Syndrome have a better prognosis than those with severe syndrome

Additional and Relevant Useful Information for Branchiootorenal/Branchiootic Syndrome:

Please visit our Kidney & Bladder Health Center for more physician-approved health information:


What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Aug. 1, 2016
Last updated: Sept. 23, 2021