Re-Examining the Cochlea in Branchio-Oto-Renal Syndrome: Genotype-Phenotype Correlation
J. Pao, Felice D’Arco, Emma Clement, Stefania Picariello, Gul Moonis, Caroline D. Robson, Amy F. Juliano
Abstract
<h3>BACKGROUND AND PURPOSE:</h3> Temporal bone imaging plays an important role in the work-up of branchio-oto-renal syndrome. Previous reports have suggested that the unwound or offset cochlea is a highly characteristic marker for branchio-oto-renal syndrome. Our goals were to examine the prevalence of this finding in a branchio-oto-renal syndrome cohort and analyze genetic-phenotypic associations not previously established. <h3>MATERIALS AND METHODS:</h3> This multicenter retrospective study included 38 ears in 19 unrelated individuals with clinically diagnosed branchio-oto-renal syndrome and confirmed mutations in the <i>EYA1</i> or <i>SIX1</i> genes. Two blinded neuroradiologists independently reviewed and documented temporal bone imaging findings in 13 categories for each ear. Imaging phenotypes were correlated with genotypes. <h3>RESULTS:</h3> There was excellent interrater agreement for all 13 phenotypic categories (κ ≥ 0.80). Of these, 9 categories showed statistically significant differences between patients with <i>EYA1</i>-branchio-oto-renal syndrome and <i>SIX1</i>-branchio-oto-renal syndrome. Cochlear offset was present in 100% of patients with <i>EYA1</i>-branchio-oto-renal syndrome, but in only 1 ear (12.5%) among patients with <i>SIX1</i>-branchio-oto-renal syndrome. A short thorny appearance of the cochlear apical turn was observed in most patients with <i>SIX1</i>-branchio-oto-renal syndrome. <h3>CONCLUSIONS:</h3> An offset cochlea is associated with the <i>EYA1</i>-branchio-oto-renal syndrome genotype. The <i>SIX1</i>-branchio-oto-renal syndrome genotype is associated with a different cochlear phenotype that almost always is without offset and has a short thorny tip as the apical turn. Therefore, cochlear offset is not a characteristic marker for all patients with branchio-oto-renal syndrome. The lack of a cochlear offset in a patient with clinically suspected branchio-oto-renal syndrome does not exclude the diagnosis and, in fact, may be predictive of the <i>SIX1</i> genotype.