Re-Examining the Cochlea in Branchio-Oto-Renal Syndrome: Genotype-Phenotype Correlation

Area of Science:

• Radiology
• Genetics
• Otolaryngology

Background:

• Branchio-oto-renal syndrome (BORS) is a genetic disorder affecting development of the ear, branchial arches, and kidneys.
• Temporal bone imaging is crucial for diagnosing BORS, with cochlear anomalies previously considered a hallmark.
• The association between specific cochlear malformations and BORS genotypes requires further investigation.

Purpose of the Study:

• To determine the prevalence of cochlear offset in a cohort of BORS patients.
• To analyze genetic-phenotypic correlations between BORS genotypes (EYA1 vs. SIX1) and temporal bone imaging findings.
• To clarify the diagnostic utility of cochlear offset in BORS.

Main Methods:

• Retrospective analysis of temporal bone imaging in 19 unrelated individuals with clinically diagnosed BORS and confirmed EYA1 or SIX1 mutations.
• Independent review of 13 imaging categories by two neuroradiologists across 38 ears.
• Correlation of imaging phenotypes with specific gene mutations.

Main Results:

• Excellent interrater agreement (κ ≥ 0.80) was achieved for all imaging categories.
• Cochlear offset was present in 100% of EYA1-BORS cases, but only 12.5% of SIX1-BORS cases.
• A short, thorny apical turn was characteristic of SIX1-BORS, while EYA1-BORS consistently showed cochlear offset.

Conclusions:

• Cochlear offset is strongly associated with the EYA1 genotype in BORS.
• The SIX1 genotype presents a distinct cochlear phenotype, typically lacking offset and featuring a thorny apical turn.
• Cochlear offset is not a universal marker for BORS; its absence may suggest the SIX1 genotype.