Branchio-oto-renal syndrome

Overview

Branchio-oto-renal (BOR) syndrome is a rare genetic disorder that affects the development of the ears, neck, and kidneys. It is characterized by abnormalities of the branchial arches (leading to neck cysts or fistulas), hearing loss, and structural or functional kidney defects. The severity and specific features of BOR syndrome vary widely among affected individuals, even within the same family. It is inherited in an autosomal dominant pattern and is one of the most common genetic syndromes associated with hearing impairment and kidney anomalies.

Causes

BOR syndrome is caused by mutations in one of several genes involved in embryonic development, primarily:

• EYA1 – the most common gene associated with BOR syndrome

• SIX1 – a gene that works alongside EYA1 in the development of ear and kidney tissues

• SIX5 – less frequently involved

The condition is inherited in an autosomal dominant manner, meaning only one copy of the altered gene is sufficient to cause the disorder. In some cases, the mutation arises de novo (spontaneously), without a family history.

Symptoms

Symptoms of BOR syndrome vary in severity but typically involve a combination of:

• Branchial anomalies:

  • Branchial cleft cysts, fistulas, or sinuses in the neck or below the ears

• Ear abnormalities:

  • Malformed external ears (lop ears, preauricular pits or tags)

  • Abnormal middle or inner ear structures

  • Hearing loss – conductive, sensorineural, or mixed, often bilateral

• Renal abnormalities:

  • Kidney hypoplasia (small kidneys) or dysplasia (abnormal structure)

  • Unilateral or bilateral renal agenesis (missing one or both kidneys)

  • Chronic kidney disease or impaired renal function

• Other possible findings:

  • Facial asymmetry

  • Palate abnormalities

Diagnosis

Diagnosis of BOR syndrome is based on clinical features, family history, and confirmatory genetic testing. Diagnostic steps include:

• Physical examination – to identify ear, neck, and facial anomalies

• Hearing tests (audiometry) – to evaluate the type and extent of hearing loss

• Renal ultrasound or imaging – to assess kidney structure and function

• Genetic testing – for mutations in EYA1, SIX1, or SIX5

• Family history assessment – to determine inheritance and identify at-risk relatives

Treatment

Treatment for BOR syndrome is multidisciplinary and focused on managing the specific symptoms present in each individual. Interventions may include:

• Hearing management:

  • Hearing aids or cochlear implants for significant hearing loss

  • Speech therapy and educational support

• Surgical procedures:

  • Excision of branchial cysts or fistulas

  • Reconstructive surgery for ear anomalies if needed

• Renal care:

  • Regular monitoring of kidney function

  • Treatment of kidney-related complications (e.g., hypertension, proteinuria)

  • Dialysis or kidney transplantation in cases of kidney failure

• Genetic counseling – for affected individuals and family members considering future pregnancies

Prognosis

The long-term outlook for individuals with BOR syndrome depends on the severity of symptoms, particularly the degree of hearing loss and kidney involvement. With appropriate medical and surgical management, many individuals lead normal, healthy lives. Early diagnosis and intervention are critical to managing hearing impairment and preventing or delaying kidney complications. Regular monitoring and a coordinated care approach can significantly improve quality of life for those with BOR syndrome.