The Cochlea in Branchio-Oto-Renal Syndrome: An Objective Method for the Diagnosis of Offset Cochlear Turns

Abstract

Background and purpose: An "unwound" or "offset" cochlea has been described as a characteristic imaging feature in patients with branchio-oto-renal syndrome, and recently recognized to be associated in particular to those with EYA1 gene mutations. Determination of this feature has traditionally relied on subjective visual assessment. Our aim was to establish an objective assessment method for cochlear offset (the cochlear turn alignment ratio) and determine an optimal cutoff turn alignment ratio value that separates individuals with EYA1-branchio-oto-renal syndrome from those with SIX1-branchio-oto-renal syndrome and healthy controls.

Materials and methods: Temporal bone CT or MR imaging from 40 individuals with branchio-oto-renal syndrome and 40 controls was retrospectively reviewed. Cochlear offset was determined visually by 2 independent blinded readers and then quantitatively via a standardized technique yielding the cochlear turn alignment ratio. The turn alignment ratio values were compared between cochleae qualitatively assessed as "not offset" and "offset." Receiver operating characteristic analysis was used to determine the ability of the turn alignment ratio to differentiate between these populations and an optimal cutoff turn alignment ratio value. Cochlear offset and turn alignment ratio values were analyzed for each branchio-oto-renal syndrome genotype subpopulation and for controls.

Results: The turn alignment ratio can accurately differentiate between cochleae with and without an offset (P < .001). The optimal cutoff value separating these populations was 0.476 (sensitivity = 1, specificity = 0.986, J = 0.986). All except 1 cochlea among the EYA1-branchio-oto-renal syndrome subset and all with unknown genotype branchio-oto-renal syndrome had a cochlear offset and a turn alignment ratio of <0.476. All except 1 cochlea among the SIX1-branchio-oto-renal syndrome subset and all controls had no offset and a turn alignment ratio of >0.476.

Conclusions: There is a statistically significant difference in turn alignment ratios between offset and nonoffset cochleae, with an optimal cutoff of 0.476. This cutoff value allows excellent separation of EYA1-branchio-oto-renal syndrome from SIX1-branchio-oto-renal syndrome and from individuals without branchio-oto-renal syndrome or sensorineural hearing loss. The turn alignment ratio is a reliable and objective metric that can aid in the imaging evaluation of branchio-oto-renal syndrome.

FIG 1.

Assessment of TAR of the cochlea on a patient without BOR (A–C) and a patient with EYA1-BOR (D–F). Standardized reformatted axial images are utilized, in which the planes are parallel to the plane of the lateral semicircular canal (A and D). Line a (green) is drawn parallel to the long axis of the basal turn (B and E), which is propagated across all axial images, including those where the apical or uppermost developed turn is visible (C and F). The midpoint of the uppermost turn is identified on the image that best displays it (black arrows in C and F); this point (point b) can also be propagated across all axial images. Line c (blue) is then drawn through point b (black arrow), perpendicular to line a (green). Distance d (between the anterior round window and the point of intersection, in yellow) and distance e (between medial bend of basal turn and the point of intersection, in red) are measured. TAR is e/d. As can be seen on these images, TAR in the patient with EYA1-BOR (F) is smaller than in the patient without BOR (C).

FIG 2.

A, Fifths of a cochlea, as demonstrated on a 3D reconstruction of the inner ear from a heavily T2-weighted sequence (3D DRIVE). The first fifth is in red (including the hook region), the second fifth in orange, the third fifth in blue, the fourth fifth in green, and the fifth fifth in black. (B, C, and D). CT of the temporal bone in a bone algorithm in the Stenvers view (B) and axial (C and D) planes shows the fifths of the cochlea in the same color scheme as depicted on the 3D model in A.

FIG 3.

Cochlear TAR among cochleae-deemed offset and not offset on visual assessment. EYA1-BOR: black round dots; SIX1-BOR: black square dots; unknown genotype: gray rhomboid dots; controls: gray triangle dots. The dashed line indicates the TAR cutoff (0.476) as determined by ROC curve analysis.

FIG 4.

ROC curve.

FIG 5.

Cochlear TAR among individuals with EYA1-BOR, SIX1-BOR, BOR of unknown genotype, and controls without BOR or sensorineural hearing loss. The TAR cutoff of 0.476 was determined by ROC curve analysis. All except one of the EYA1-BOR cochleae have TAR below the cutoff value. All except one of the SIX1-BOR cochleae have TAR above the cutoff value. All individuals with BOR of unknown genotype have TAR below the cutoff value. None of the controls have TAR below the cutoff value.

FIG 6.

Axial CT images of 3 different patients with EYA1-BOR showing the anteriorly offset unwound cochlea, an imaging feature characteristic of EYA1-BOR. Notice that the middle and apical turns are anteriorly located relative to the basal turn (red arrows) and slightly tilted away and separated from the basal turn (yellow arrowheads).

FIG 7.

CT image of the patient with SIX1-BOR in whom the right cochlea does not demonstrate any offset (long arrow), while the left cochlea has an offset but with an appearance akin to cochlear hypoplasia type 4 rather than the typical unwound and offset cochlea of EYA1-BOR. Notice the normal size and morphology of the basal turn first half (short arrow), while the distal basal, middle, and apical turns are hypoplastic (arrowhead).

FIG 8.

A thorny apical turn in a patient with SIX1-BOR. The apical turn of the cochlea appears as a short, protuberant, thorny tip, as seen on CT (A) and MR imaging (B).