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phenotype, natural history, and genetic etiology remain

unclear. The underlying goal of the present study was to

shed light on these areas of uncertainty and to deter-

mine the clinical significance of unilateral EVA in

pediatric patients.

Overall, the patients in this study demonstrated

an extremely heterogeneous audiometric phenotype.

Patients with unilateral EVA as well as those with bilat-

eral EVA had unilateral and bilateral hearing loss and

varying levels of hearing loss severity. Interestingly, we

found no difference in hearing loss severity between the

unilateral and bilateral EVA cohorts. This finding

implies that the inner ear dysfunction in patients with

bilateral EVA is not necessarily more severe than the

dysfunction in patients with unilateral EVA.

In patients with unilateral EVA, there was no corre-

lation between the side of the hearing loss and the side of

the EVA, as

50% of patients with unilateral EVA had

contralateral hearing loss. Furthermore, these patients

showed no difference in hearing loss severity between the

contralateral and ipsilateral ears. These findings suggest

that unilateral EVA may be a phenotypic expression of

bilateral alterations in the membranous labyrinth and

that unilateral EVA is likely not a unilateral disease pro-

cess. The latter conclusion can perhaps be explained by

events that occur during embryogenesis. Specifically, per-

turbation of the inner ear labyrinth, which causes

endolymphatic duct dilatation, can occur after embryonic

temporal bone mesenchyme condenses into bone; hence,

imaging would not reveal enlargement of the vestibular

aqueduct. Alternatively, if endolymphatic duct dilatation

occurs earlier in embryogenesis, imaging studies would

reveal the enlargement of the vestibular aqueduct.

Data pertaining to temporal bone phenotypes show a

correlation between the final PTA and midpoint and oper-

culum measurements and the HFPTA and midpoint and

operculum measurements. This correlation has not been

previously established. Studies conducted by Zalzal et al.

and Colvin et al.

reported no relationship between the

absolute level of hearing or hearing loss progression and

temporal bone measurements; however, both studies used

more restrictive criteria for EVA (i.e., a midpoint measure-

ment 1.5 mm) and had small study populations.

Reporting on 77 patients, Madden et al.

found a relation-

ship between the midpoint and operculum measurements

and the rate of progression, but not with the initial PTA.

The disparity between historical findings and the present

study may be attributed to our use of a final PTA measure-

ment, which may have been affected by the presence of

progressive hearing loss.

Patients with unilateral EVA had slightly better

hearing compared to those with bilateral EVA, although

this difference was not statistically significant. The

difference may be related to the relatively high preva-

lence of isolated high-frequency hearing loss in patients

with unilateral EVA. Overall, a comparison of temporal

bone measurements in patients with unilateral and

bilateral EVA revealed no critical differences. Neverthe-

less, subtle differences were evident. Specifically,

although operculum measurements were larger in

patients with unilateral EVA, there was no difference in

midpoint measurements between patients with unilat-

eral and bilateral EVA. Also, patients with unilateral

EVA and ipsilateral hearing loss had larger vestibular

aqueduct measurements than patients with bilateral

EVA, suggesting the possibility of a different underlying

etiology between the two groups.

Hearing loss progression was seen both in patients

with unilateral EVA and in patients with bilateral EVA.

Although it was more commonly seen in patients with

bilateral EVA, this difference was not statistically signifi-

cant. This lack of significance remained constant when

analyzing ears with unilateral and bilateral hearing loss.

Interestingly, patients with unilateral EVA had a

similar rate of progression in both the ipsilateral and

contralateral ears. When compared to the ears in

patients with unilateral hearing loss without EVA, the

ears of patients with unilateral EVA had a higher likeli-

hood of progression. In patients with unilateral hearing

loss without EVA, only 6% had involvement of the con-

tralateral ear. In sharp contrast, 55% of patients with

unilateral EVA had involvement of the contralateral ear.

Collectively, these data support our study hypothesis

that patients with unilateral EVA would have a much

higher rate of contralateral hearing loss than patients

with unilateral hearing loss without EVA.

In patients with EVA, hearing loss at 250 Hz is

strongly correlated with the severity of the PTA and the

likelihood of progression. Additionally, the hearing loss

TABLE VII.

Rate of Progression Based on Audiometric Phenotype and

SLC26A4

Testing Results by Patient.

Progression in Unilateral EVA, n

54 Bilateral EVA, n

Both ears

6 (11%)

11 (20.4%)

.18

Only one ear

15 (27.8%)

19 (35.2%)

No ears

33 (61.1%)

24 (44.4%)

Rate of Progression

SLC26A4

Positive

SLC26A4

Negative

All patients with EVA

10/17 (58.8%) 22/48 (45.8%) .36

Patients with unilateral EVA 0/3

13/27 (48.2%) .24*

Patients with bilateral EVA 10/14 (71.4%)

9/21 (42.9%) .10

*Fisher exact test.

EVA

enlarged vestibular aqueduct.

TABLE VIII.

Rate of Progression Based on Audiometric Phenotype and

SLC26A4

Testing Results by Ears.

SLC26A4

Positive

SLC26A4

Negative

Ears with HL

14/27 (51.9%)

26/73 (35.6%)

.14

Ears with HL

EVA 14/26 (53.9%)

20/59 (33.9%)

.08

Ears with HL

unilateral EVA

0/2

10/24 (41.7%)

.51*

Ears with HL

bilateral EVA

14/24 (58.3%)

10/35 (28.6%)

.02

*Fisher exact test.

EVA

enlarged vestibular aqueduct; HL

hearing loss.

Laryngoscope 123: June 2013

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