Branchiootorenal (BOR) Syndrome: Oral Symptoms

Introduction:

Branchiootorenal syndrome (BOR) is the autosomal dominant syndrome (a genetic condition when a gene on a non-sex chromosome is passed from parent to child) or disease condition caused by genetic mutations. Medical research has described this condition as a branchial arch disorder during the embryogenesis phase (differentiation of cells from the zygote into three cell layers) in the developing fetus that leads to the disordered formation of the neck. However, there are several other oral, head, and neck manifestations associated with this genetic mutation-based syndrome. This is a rare disease but severe in terms of systemic affliction to the patients or the newborns affected. As of current global statistics, the incidence rate of this genetic mutation-based syndrome is around 1 case for every 40,000 newborns, as observed or documented in medical literature in Western countries.

What Are the Causes of Branchiootorenal Syndrome?

The EYA1 gene mutation causes BOR syndrome. Although other gene mutations, such as the SIX 1 and SIX 5 mutations, may also contribute to BOR, this is the most often implicated gene mutation. According to the etiological factors causing this syndrome, both kidney-based renal abnormalities and hearing disorders are caused by point mutations or deletions in the sequence of the gene on the long arm of chromosome 8 in affected individuals. This gene essentially encodes for the transcription factor known as EY (factor essential for eye development). The majority of the head and neck symptoms observed in individuals with this genetic mutation are caused by anomalies in the second branchial arch (a paired structure that formed into the face, neck, and oropharynx) during the embryonic stage.

Why BOR Syndrome Is Underestimated in Terms of Orofacial Manifestations?

To determine the manifestations on the head, neck, and face regions, this condition has now been well-studied in the literature on oral and maxillofacial surgery. Although doctors and neonatologists would typically diagnose this condition, a maxillofacial surgeon would typically be the only one to diagnose the unexplored side or the symptoms related to the head, neck, and mouth. For example, patients may have various oral, head, and neck symptoms, but doctors may not focus on these areas since they need to work with the maxillofacial surgeon in an interdisciplinary manner.

What Are the Oral and Maxillofacial Manifestations of Branchiootorenal Syndrome?

Firstly, the major clinical affliction is the improper branchial arch functions that affect neck formation. This results in the formation of fistulas or cysts in the neck regions. A cyst is a pathologic cavity comprising a sac or pocket of tissue that can be filled with air, pus, infected cells, or debris - on the other hand; a fistula is completely different. A fistula is a passageway that forms a two-way communication between two viral structures in the body. In the case of the BOR syndrome, the affected individuals show a common presence of neck fistulae that can give the maxillofacial surgeon a diagnostic suspicion of the same. Hence, both neck fistulae and deformities that can be observed in the inner or outer ear, along with skin pits or tags on the skin, indicate a diagnosis of this syndrome. Further, one or both of the patient's kidneys may be infected or affected severely. Though this syndrome can be managed by the maxillofacial surgeon and the physician, because of the genetic complications and the complex nature of this condition, end-stage renal disease (ESRD is the final stage of chronic kidney disease when the kidney no longer functions) can commonly occur at later phases of life despite the implementation of treatment strategies early in life or infancy.

What Are the Clinical Features of BOR?

The maxillofacial surgeon then needs to collaborate with the physician to check for the other clinical signs and symptoms associated commonly with this syndrome, such as :

• Mis-shapen ears.

• Facial asymmetry.

• Deafness or hearing loss (partially or totally).

• Malformations in the ear.

• Outer ear pits are also called preauricular pits.

• Outer ear tags are also called preauricular tags.

• Structural defects that occur in the middle ear.

• Structural defects that occur in the inner ear.

Systemic Features: Correlating further to the systemic features clinically exhibited by the patient, such as major loss of kidney functions owing to defects in kidney structure and respiratory pathologies leading to obstruction of the patient airway.

How Is BOR Diagnosed?

A diagnosis can be formulated clinically upon examination of BOR.

Usually, the BOR syndrome may be familial in origin, though medical research has not shed much light on the origin of the second branchial arch abnormalities because of the EY gene mutation. However, confirmation of clinical features is possible, and correlation, especially with kidney defects and kidney disease, with hearing loss, can help confirm the diagnosis.

The differential diagnosis for this syndrome would be branchio-oculo-facial syndrome (a genetic disorder that affects the neck, face, and eyes before birth) and Goldenhar syndrome (the congenital condition that affects the face, eyes, ears, and spine).

What Are the Management Aspects of BOR?

Through interdisciplinary collaboration with the otolaryngologist, neonatologist, and physician, the maxillofacial surgeon may undoubtedly play a significant role in identifying, managing, and following treatment protocols for this uncommon but severe genetic syndrome.

Apart from the observations by the maxillofacial surgeon, even dentists can commonly detect this syndrome upon keen observation owing to the presence of labial commissure pits or lip pits that accompany the auricular and renal structural deformities. The management, hence, depends on an interdisciplinary collaboration between different specialists and the operating surgeon to restore the patient's facial form function, as well as renal monitoring that can improve the overall prognosis. As the second branchial arch abnormalities cause severe oral, facial, head and neck, ear, and renal manifestations in the afflicted are often accompanied by superinfections at different phases of life, management is hence frequently done by antibiotic therapies only.

While kidney transplantation and renal surgical management are needed for kidney disease (along with dialysis if required), management of oral pits, palatal abnormalities, and neck fistulae by the maxillofacial surgeon and hearing loss correction by tympanoplasty or cochlear implants that can be placed to correct the disorder. These are the varying management aspects by each surgeon in the treatment of this complex multiple systemic organ targeting condition.

Conclusion:

To conclude thus, BOR syndrome is not only just a renal disease that is caused by genetic mutations, but it is also an oral and maxillofacial condition that requires a lot of interdisciplinary support and intense collaboration by different specialists. Timely management of these maxillofacial abnormalities by the maxillofacial surgeon and referral to the appropriate specialists for managing the multi-organ clinical symptoms would make the patient's systemic functions easier, improving the quality of life.