Branchio-oto-renal syndrome (also known as branciootorenal syndrome, BOR syndrome or BOR, Melnick- Fraser Syndrome) is an autosomal dominantgenetic disorder involving the kidneys, ears, and neck. 90% of these are due to inheritance and in 10% cases, it is acquired mutation. It is characterized by the presence of 1) brachial fistulae or cysts; 2) Ear malformations - including outer, middle or inner ear; 3) Renalmalformations, which can range from renalhypoplasia to renal agenesis. The most important differential studied is Branchiootic syndrome (BO) which has exactly the same features as BOR syndrome but the affected individuals do not have the kidneys abnormalities like in BOR syndrome. The two condition similarities some times create a hard time for researchers. Sometimes they even consider them together as BOR/BO syndrome.
"Branchio-" means the second branchial arch, s structure that is usually present in the embryo that further gives rise to tissues on the front and the side of the neck. The abnormal development of this branchial arch leads to leads to the formation of neck masses called branchial cleft cysts which is most commonly seen in people with BO/BOR syndrome. Some people might have abnormal appearing pits or holes in the side of the neck called fistulae. They can form a connection with the mouth near the tonsil. Both branchial cleft cyst and fistulae can create problems later in life so they are usually removed during the early stages of childhood. "Oto-" refer to the ear. It has been studied that most patients with BO/BOR syndrome usually have hearingabnormalities. It can be sensorineural, conductive, or mixed. Sensorineuralhearing loss is usually seen in the patients with abnormalities in the inner ear: conductive hearing loss is due to the defects of bones in the middle ear; Mixed hearing loss is caused by both inner ear + middle ear abnormalities. Preauricular pits ( tiny holes) and tags (an extra bit of tissue) are the other anomalies associated with the ear anomalies. "Renal" word means kidneys here; The major point to be noted here is that BO syndromes do not have real components. So BOR syndrome causes an alteration in kidneystructure and function. The renalabnormalities range from mild to severe and may include one or both the kidneys. The renal abnormalities include the complete absence of kidneys in some cases while in others only mild hypoplasia is present. The most serious condition associated with kidneys is their inability to clear fluids and waste from the body which is usually given a name End-stage renal disease(ESRD).
Autosomal dominant pattern of inheritance observed in BOR Syndrome.[2]
90% of BOR syndromes result from inheritance and 10% of the cases are thought to be the result of acquired mutations. Branciootorenal syndrome has an Autosomal dominant inheritance pattern with variable expressivity as a result of which the same family members express the different levels of severity of the disease. It also shows a 100% penetrance. The mutations in the genes - SIX1, EYA1, and SIX5 play a major role in the causation of BOR syndrome. Out of these, EYA1 gene mutations play a major role (40%) followed by the SIX1 gene, and SIX5genemutation is only found in a small number of people suffering from BOR syndrome.
The proteins produced from these genes play a major role in the development before birth. Interaction of EYA1 protein with SIX5 and SIX1 modulates the genes involved in embryonic development. These interactions also play a major role in the development of the ear, kidneys, and second branchial arch. The latter organs are mainly involved in the Branciootorenal syndrome.
Differentiating Branchio-oto-renal syndrome from other Diseases
The symptoms of the following disorders can be overlapping with symptoms of Branchio-renal syndrome. comparison is important to make the relevant differential diagnosis:
If no evidence of family history then clinicalcriteria should be used to make the diagnosis, Either:
3 Major
2 Major plus 2 Minor criteria
Diagnostic criteria for BOR Syndrome ( 2 major /or 2 major + 2 minor)
MAJOR CRITERIA
MINOR CRITERIA
Hearing loss
Middle ear anomalies
Renal anomlies
Inner ear anomalies
2nd Branchial arch anomlies
Euthyroid goiter
Pinnae malformation
Preauricular tags
Preauricular pits
Lacrimal duct aplasia
External auditory canal anomlies
Facial asymmetry/palate abnormalities
Management and Treatment
Management
Most Important component in managing a patient with Branchio-oto-renal syndrome is the evaluation of involved organs carefully. The following table shows the organs needed to be evaluated and what a medical practitioner needs to focus on while managing the patient of BOR syndrome
![[1]](https://radiologykey.com/wp-content/uploads/2015/12/B9780323081764001130_t0015.png){kind=link}
![[2]](https://en.wikipedia.org/wiki/Branchio-oto-renal_syndrome#/media/File:Autosomal_dominant_-_en.svg){kind=link}