Clinical characteristics: Branchiootorenal spectrum disorder (BORSD) is characterized by malformations of the outer, middle, and inner ear associated with conductive, sensorineural, or mixed hearing impairment, branchial fistulae and cysts, and renal malformations ranging from mild renal hypoplasia to bilateral renal agenesis. Some individuals progress to end-stage renal disease (ESRD) later in life.
Extreme variability can be observed in the presence, severity, and type of branchial arch, otologic, audiologic, and renal abnormality from right side to left side in an affected individual and also among individuals in the same family.
Diagnosis/testing: The diagnosis of branchiootorenal spectrum disorder is based on clinical criteria. The diagnosis is established in a proband with the clinical features and/or heterozygous pathogenic variants in EYA1, SIX1, or SIX5 identified on molecular genetic testing.
Management: Treatment of manifestations: Excision of branchial cleft cysts/fistulae, fitting with appropriate aural habilitation, and enrollment in appropriate educational programs for the hearing impaired are appropriate. A canaloplasty should be considered to correct an atretic external auditory canal. Medical and surgical treatment for vesicoureteral reflux may prevent progression to end-stage renal disease (ESRD). ESRD may require renal transplantation.
Surveillance: Semiannual examination for hearing impairment and annual audiometry to assess progression of hearing loss; monitoring of renal function to prevent progression to ESRD; semiannual/annual examination by a nephrologist and/or urologist, as indicated.
Agents/circumstances to avoid: Nephrotoxic medications.
Evaluation of relatives at risk: At-risk relatives should be screened for hearing loss and renal involvement to allow for early diagnosis and treatment.
Genetic counseling: BORSD is inherited in an autosomal dominant manner. The offspring of an affected individual are at a 50% risk of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
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