Paediatric Laboratory Medicine
Paediatric Laboratory Medicine
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Hearing Loss: Branchio-Oto-Renal (BOR) Syndrome

Background
Who should be tested?
Testing Methodology
Potential Outcomes & Interpretation of Test Results
Cautions
For More Information

Background

Branchio-oto-renal (BOR) syndrome is an autosomal dominant condition characterized by branchial, otic and renal anomalies. Branchial arch defects include cysts and fistulae. Otologic findings include sensorineural, conductive or mixed hearing loss with malformations of the outer, middle and inner ear. Renal malformations range from mild renal hypoplasia to bilateral renal agenesis, with some individuals progressing to end-stage renal disease later in life. Patients with BOR syndrome may show variability in clinical features due to incomplete penetrance and variable expressivity.

BOR syndrome is genetically heterogeneous; however, mutations in the EYA1 gene at 8q13.3 have been implicated in about 40 per cent of BOR syndrome cases. Of BOR syndrome patients with EYA1 mutations, approximately 75–80 per cent have point mutations in the EYA1 gene while the remainder may have rearrangements of the gene causing large deletions or insertions. Molecular testing for BOR syndrome consists of complete sequencing of the coding region and flanking exon/intron boundaries of the EYA1 gene to detect point mutations, and quantitative testing of the EYA1 gene to detect larger deletions or duplications.

BOR syndrome is present when an individual has one copy of the defective EYA1 gene. Affected individuals have a 50 per cent chance of transmitting the disorder to each child. There is a 50 per cent chance that the affected individual’s offspring will not be affected with BOR syndrome.

Who should be tested

  • individuals clinically suspected of being affected with BOR syndrome
  • relatives of probands with identified EYA1 mutations
  • pregnancies at risk due to a family history of BOR syndrome

Testing Methodology

Direct Mutation Analysis:

  • Direct sequencing to identify point mutations in the EYA1 gene
  • Quantitative testing of the EYA1 gene for large deletions or duplications

Test Sensitivity: Approximately 40 per cent of clinically diagnosed BOR patients have point mutations or large deletions/duplications in the EYA1 gene. As BOR is a genetically heterogeneous disorder, mutations in genes other than EYA1 may also cause BOR syndrome. A negative result does not rule out the possibility that the individual is affected with BOR and has a mutation in EYA1, or in a different gene causing BOR, not detected in this assay.

Potential Outcomes & Interpretation of Test Results

Reason for
referral

EYA1 Gene
Mutations

Explanation

diagnosis

none detected

  • This result does not support a diagnosis of BOR syndrome

diagnosis

mutation detected

  • This result is unable to confirm a diagnosis of BOR syndrome


Cautions

  • Current molecular testing will not detect all possible mutations causing BOR syndrome. A negative result does not rule out the possibility that the individual has an EYA1 mutation not detected by the current assays, or a mutation in another gene associated with BOR syndrome, and is affected with BOR syndrome.
  • Test results should be interpreted in the context of clinical findings, family history and other laboratory data.
  • These tests were developed and the performance characteristics validated by the Molecular Genetics Laboratory at the Hospital for Sick Children. They have not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes.

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