Table 2.
Vestibular Findings in Families with Known DFNA Gene Mutations
| Locus/Gene | Reference | Mutation | Testing Method & # of Individuals Tested | Findings | Author Conclusion/Comment |
|---|---|---|---|---|---|
| CRYM | 1 | p.K314T, p.X315Y | Caloric on 1 affected person with the X315Y mutation. | Normal caloric. | No vestibular involvement for all affected individuals. |
| ESPN | 11 | p.S719R
p.D744N p.delK848 |
Routine vestibular tests. 1–2 individuals tested per mutation. | No vestibular involvement. | No vestibular involvement. |
| DFNA1, DIAPH1 | 20 | Splice donor, gt-to-gg, FS | Caloric, VAT, & oculomotor. 3 affected individuals tested. | All normal, except 1 person with unilateral caloric weakness. | None of the affected members report vestibular disturbances. |
| DFNA2, KCNQ4 | 21 | p.W276S | Caloric, VST, & oculomotor.
37 affected individuals tested. |
3 of 37 showed unilateral caloric weakness.
13 of 37 showed VOR hyperactivity, 4 of these 13 reported motion sickness, 1 of these 13 reported transient vertigo. 1 of the other 37 also reported transient vertigo. Oculomotor normal except for 1 of 37. |
Vestibular system was functional throughout life of these patients. No bilateral caloric weakness. VOR hyperactivity is puzzling, may be a central abnormality. |
| 2 | p.W276S | Caloric.
5 affected individuals tested. |
1 of 5 showed unilateral caloric weakness.
2 of 5 reported vertigo. 1 of 5 reported an epilepsy episode. |
Further discussion needed to reach a conclusion as whether epilepsy is component of KCNQ4 mutation. | |
| 7 | p.W276S | Caloric & VST.
11 affected individuals tested. |
3 of 11 showed VOR hyperactivity, 2 of 3 reported motion sickness. 2 of 11 showed VOR hypoactivity but had normal calorics. | VOR hyperactivity may be explained by release from central inhibition. In mice, KCNQ4 is expressed in vestibular nuclei. | |
| DFNA3, GJB2 | 31 | 5 different mutations | Caloric & VEMP.
1 person w/each mutation tested |
Normal calorics, 3 of 5 with absent VEMP, 1 of these 3 reported unsteadiness. | In most cases, saccular defect is well compensated for by patient. |
| 22 | T55N | Caloric & VEMP.
6 affected individuals tested. |
5 of 6 with abnormal caloric.
4 of 6 with abnormal VEMP. |
Vestibular dysfunction associated with Cx26 mutation for first time. | |
| DFNA4, MYH14 | 23 | p.S120L | Caloric.
5 generation family. |
Normal caloric findings. | Normal caloric findings. |
| 10 | p.G376C, p.R726S, p.L976F | Do not indicate testing method.
Individuals from 3 different families. |
Hearing loss without vestibular involvement. | Hearing loss without vestibular involvement. | |
| DFNA5 | 8 | Exon 8 skip, premat. stop | Caloric & VST.
4 affected individuals tested. |
Response parameter values of 4 patients were normal w/few exceptions. | No vestibular symptoms. |
| 3 | Exon 8 skip, premat. stop | VOR.
6 affected individuals tested. |
Vestibular symptoms not self reported.
1 of 6 with hyperactive VOR. |
Vestibular function was generally normal. | |
| DFNA6/14, WFS1 | 13 | p.L829P | Caloric & oculomotor.
4 generation family. |
Oculomotor & caloric tests did not show any consistent deficits. | No significant abnormalities. |
| 19 | p.T699M | Caloric, VST, & oculomotor.
20 affected family members. |
19 of 20 w/normal oculomotor, 15 of 17 w/normal caloric, 1 of 15 w/VOR hyporeflexia, 6 of 15 showed VOR hyperreflexia. | With few exceptions, vestibular function was intact. | |
| 27 | p.G674V | Caloric, VST, & oculomotor.
2 affected family members. |
Normal oculomotor and vestibular responses. | No substantial vestibular symptoms. | |
| 32 | p.T699M | Caloric & oculomotor.
4 affected individuals tested. |
Normal oculomotor and caloric responses. | Normal vestibular responses. | |
| DFNA8/12, TECTA | 14 | p.R2021H | Caloric.
4 affected individuals tested. |
All affected members had normal vestibular function. | All affected members had normal vestibular function. |
| 28 | p.R1890C, p.T83M | VST & oculomotor.
4 affected individuals tested. |
Intact horizontal VOR, 2 people w/long time constant. Normal oculomotor.
No vestibular symptoms. |
Given TECTA is expressed in otolith membrane, otolith-testing paradigms should be considered. | |
| DFNA9, COCH | 6 | p.P51S | Do not indicate testing method.
6 affected individuals tested. |
Vestibular tests disclosed complete areflexia in 5 individuals & severe hyporeflexia in 1. | Patients experienced instability esp in dark & head movement-dependent oscillopsia. |
| 17 | p.V66G | Caloric, 3 affected individuals. | 2 with absent bithermal caloric responses.
1 with unilaterally absent caloric responses. |
Vestibular complaints. | |
| 33 | p.A119T | Caloric, 1 affected individual. | Bilateral decreased response. | Recurrent dizziness & vertigo. | |
| 24 | p.V104del | Do not indicate testing method.
1 affected individual. |
Total cochleovestibular areflexia in both ears. | Patient reports severe vertigo, nausea, & vomiting. | |
| 15 | p.G88E | Caloric, oculomotor, VST.
10 affected individuals. |
2 showed vestibular areflexia, 1 showed bilateral caloric weakness, 1 showed asymmetric responses to caloric testing. | Instability especially in dark, vertigo, & tendency to fall. | |
| 29 | p.C542F | Caloric, oculomotor, VST, SOT, VEMP, CDP
3 affected individuals tested. |
Central oculomotor dysfunction, progressive vestibular hypofunction, absent VEMP responses. | Vestibular symptoms not noticed until after the 4th decade of life. | |
| 25 | p.G87W | Caloric, oculomotor, VST.
12 affected individuals. |
2 of 10 affected individuals showed vestibular areflexia. | Instability especially in dark, vertigo, & tendency to fall. | |
| 26 | p.I109T | Caloric, oculomotor, VST.
7 affected individuals. |
1 of 7 showed complete vestibular areflexia. | Instability especially in dark, vertigo, & tendency to fall. | |
| DFNA11, MYO7A | 30 | del p.A886, K887, K888 | Caloric & spontaneous nystagmus.
5 affected individuals tested. |
3 of 5 showed caloric hyporeflexia.
3 of 5 showed spontaneous nystagmus. |
No vestibular symptoms. |
| 5 | p.R853C | Do not indicate testing method.
5 affected individuals tested. |
Mild vestibular dysfunction found in 1 of 5 patients. | Mild vestibular dysfunction found in 1 of 5 patients. | |
| 4 | N458I | Caloric & VST.
6 affected individuals tested. |
Vestibular symptoms and dysfunction reported & found in 4 of 6 patients. | Vestibular dysfunction not fully penetrant & likely progressive. | |
| 9 | p.A230V | Do not indicate testing method.
3 affected individuals tested. |
Vestibular bilateral areflexia in all 3 patients. | Minor vestibular problems. | |
| DFNA13, COL11A2 | 18 | p.G323E | Caloric & VST.
17 affected individuals tested. |
Abnormal caloric in 8 of 17, 4 of 17 w/VOR hyperactivity, all w/normal oculomotor. | No substantial vestibular impairment symptoms. |
| DFNA20/26, ACTG1 | 12 | p.T89I | Interview & neurologic exam. | No evidence of vestibular dysfunction was observed during neurologic exam. | Neither proband nor relatives report vestibular problems. |
| 16 | p.T278I | Caloric, VST, oculomotor, COR.
7 affected individuals. |
Normal calorics, 2 people with VOR hyporeflexia, 1 with enhanced COR. | No or very limited vestibular involvement. |
FS, frameshift; VAT, vestibular autorotation; VST, vestibular step test; VOR, vestibulo-ocular reflex; VEMP, vestibular evoked myogenic potential; Cx26; connexin-26; Premat., premature; SOT, sinusoidal oscillation test; CDP, computerized dynamic posturography; COR, cervico-ocular reflex