Superior Canal Dehiscence Syndrome Affecting 3 Families

This case series describes the features of superior canal dehiscence syndrome in the multiple affected members of 3 families and explores the prospect of a genetic origin.

Key Points

Question

Do familial cases of superior canal dehiscence syndrome support a molecular genetic basis for the condition?

Findings

Seven individuals in 3 families in this case series were diagnosed with superior canal dehiscence syndrome or near dehiscence. Because 5 of the 7 patients were not obese, obesity alone does not explain the occurrence of superior canal dehiscence syndrome.

Meaning

This report provides evidence in support of a potential genetic contribution to the etiology of superior canal dehiscence syndrome.

Abstract

Importance

Superior canal dehiscence syndrome (SCDS) is an increasingly recognized cause of hearing loss and vestibular symptoms, but the etiology of this condition remains unknown.

Objective

To describe 7 cases of SCDS across 3 families.

Design, Setting, and Participants

This retrospective case series included 7 patients from 3 different families treated at a neurotology clinic at a tertiary academic medical center from 2010 to 2014. Patients were referred by other otolaryngologists or were self-referred. Each patient demonstrated unilateral or bilateral SCDS or near dehiscence.

Interventions

Clinical evaluation involved body mass index calculation, audiometry, cervical vestibular evoked myogenic potential testing, electrocochleography, and multiplanar computed tomographic (CT) scan of the temporal bones. Zygosity testing was performed on twin siblings.

Main Outcomes and Measures

The diagnosis of SCDS was made if bone was absent over the superior semicircular canal on 2 consecutive CT images, in addition to 1 physiologic sign consistent with labyrinthine dehiscence. Near dehiscence was defined as absent bone on only 1 CT image but with symptoms and at least 1 physiologic sign of labyrinthine dehiscence.

Results

A total of 7 patients (5 female and 2 male; age range, 8-49 years) from 3 families underwent evaluation. Family A consisted of 3 adult first-degree relatives, of whom 2 were diagnosed with SCDS and 1 with near dehiscence. Family B included a mother and her child, both of whom were diagnosed with unilateral SCDS. Family C consisted of adult monozygotic twins, each of whom was diagnosed with unilateral SCDS. For all cases, dehiscence was located at the arcuate eminence. Obesity alone did not explain the occurrence of SCDS because 5 of the 7 cases had a body mass index (calculated as weight in kilograms divided by height in meters squared) less than 30.0.

Conclusions and Relevance

Superior canal dehiscence syndrome is a rare, often unrecognized condition. This report of 3 multiplex families with SCDS provides evidence in support of a potential genetic contribution to the etiology. Symptomatic first-degree relatives of patients diagnosed with SCDS should be offered evaluation to improve detection of this disorder.

Introduction

Superior canal dehiscence syndrome (SCDS) is a rare disorder of the inner ear that was first described by Minor et al in 1998. Symptoms associated with SCDS include hearing loss to air-conducted sounds, hyperacusis to bone-conducted sounds, aural fullness, autophony, disequilibrium, and oscillopsia with the Valsalva maneuver or exposure to loud sound. The clinical presentation varies considerably from individual to individual.

Dehiscence of bone over the superior semicircular canal is the pathologic basis for this syndrome and has been verified in a surgically created animal model of the disorder. Although there have been 3 published reports of acquired dehiscence due to erosion from a neoplasm or osteomyelitis, for all other cases the cause of the dehiscence remains unknown. A recent study found that patients with radiographic superior canal dehiscence were more likely to have had a higher mean body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) and history of obstructive sleep apnea compared with those without dehiscence. The authors proposed that elevated intracranial pressure could gradually erode bone over the superior canal, but the role of intracranial pressure remains speculative and has never been measured in this population.

Given the lack of a clear environmental cause for the bony dehiscence, the question arises whether this condition may have a genetic basis. We have identified and clinically characterized 3 families with at least 2 first-degree relatives each affected with SCDS. In 2 families, at least 1 affected relative had a BMI in the healthy range. A correlative clinical, audiologic, and radiographic analysis of each family is presented.

Methods

Since 2009, one of us (K.D.H.) has kept a log of patients diagnosed with SCDS in her practice. This log is maintained within the electronic medical record system that is compliant with security standards established by the Health Insurance Portability and Accountability Act. From this log, we have identified 3 families with more than 1 affected relative. The institutional review board of the University of Michigan approved this study, and all patients in this case series provided informed written consent.

Radiographic dehiscence was defined as the absence of bone over the superior semicircular canal on at least 2 consecutive Stenver computed tomographic (CT) projections. For 1 pediatric patient in this series, Stenver views were not available and coronal temporal bone sequences were used. The site of dehiscence was classified according to the scheme proposed by Lookabaugh et al. This radiographic classification scheme identifies the following 5 types of canal dehiscence: an arcuate eminence defect, lateral upslope defect, medial downslope defect, superior-petrosal sinus defect, and arcuate eminence defect with near-dehiscent superior petrosal sinus.

A diagnosis of SCDS was made if the patient had radiographic dehiscence on the temporal bone CT in addition to at least 1 physiologic sign consistent with labyrinthine dehiscence. Acceptable physiologic signs include eye movements that align in the plane of the superior semicircular canal with loud sound (Tullio phenomenon) or pressure changes in the external auditory canal (Hennebert sign), conductive hearing loss of at least 10 dB ranging from 250 to 4000 Hz, a ratio of the summating potential (SP) to the action potential (AP) of at least 0.40 by tympanic electrocochleography, or abnormal cervical vestibular evoked myogenic potential (VEMP) result. At our institution, we typically classify the cervical VEMP threshold of 65 dB or less as low and consistent with canal dehiscence, 75 dB as equivocal, and 85 dB as normal. However, if the cervical VEMP threshold is equivocal or normal but the amplitude of the p13-n23 potential is more than 1.3 times as large on the side of a dehiscence, we also consider this to be a positive physiologic sign. Although ocular VEMP has been reported to be very sensitive for detection of SCDS, we do not have ocular VEMP data for the patients described herein because our neurodiagnostic testing battery for SCDS includes cervical VEMP and electrocochleography. Electrocochleography was obtained by using a tympanic membrane surface electrode placed under binocular otomicroscopic observation. Alternating clicks presented at 90- to 95-dB normal hearing level are used as stimuli. Response recording is preceded by a prestimulus baseline serving as the reference for SP and AP amplitude measurements. Typically, 2 responses are combined into a grand mean, which is then used for the relevant amplitude measurements and SP:AP ratio calculation. Near dehiscence was defined as the absence of bone over the superior semicircular canal on only 1 CT image but with symptoms and at least 1 physiologic sign of labyrinthine dehiscence.

Clinical Presentation

Because the patients described in this article underwent evaluation during a 4-year period, the age and BMI reported for each patient were from the time a diagnosis of SCDS was made. Body mass index for patients 20 years or older was classified according to the Centers for Disease Control and Prevention guidelines, in which less than 18.5 is underweight; 18.5 to 24.9, normal weight; 25.0 to 29.9, overweight; and 30.0 or more, obese. For patients aged 2 to 19 years, the Centers for Disease Control and Prevention BMI percentile calculator was used to determine whether the patient’s weight was considered to be healthy. Each family is presented and data are summarized in the Table.

Table. Summary of Patient Radiographic and Neurodiagnostic Test Results.

Family-Patient No./Age Decade, y	BMI	BMI Classa	Ear	Superior Semicircular Canal on CT	Cervical VEMP Threshold, dB	ECOG Finding, SP:AP Ratio
A-1/20s	20.4	Normal	Right	Arcuate eminence defect	75-85	0.18
			Left	Arcuate eminence defect	65	0.59
A-2/40s	28.1	Overweight	Right	Arcuate eminence defect	65	1.30
			Left	Thin bone over lateral upslope	65	0.80
A-3/20s	26.9	Overweight	Right	Thin bone over arcuate eminence	65	0.68
			Left	Normal	75	0.38
B-1/<10	16.9	70th Percentile (normal)	Right	Normal	80	Not obtained
			Left	Arcuate eminence defect	80b	Not obtained
B-2/40s	27.2	Overweight	Right	Arcuate eminence defect	90	0.11
			Left	Arcuate eminence defect	65-70	0.42-0.63
C-1/40s	39.1	Obese	Right	Normal	85	0.35
			Left	Arcuate eminence defect	65	0.72
C-2/40s	30.3	Obese	Right	Arcuate eminence defect	65	0.83
			Left	Normal	65	0.80

Abbreviations: AP, action potential; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CT, computed tomography; ECOG, electrocochleography; SP, summating potential; VEMP, vestibular evoked myogenic potential.

^aClassified for patients 20 years or older according to the Centers for Disease Control and Prevention guidelines, in which less than 18.5 is underweight; 18.5 to 24.9, normal weight; 25.0 to 29.9, overweight; and 30.0 or more, obese. For pediatric patients, the Centers for Disease Control and Prevention BMI percentile calculator was used to determine whether the patient’s weight was considered to be healthy or not. A BMI of the fifth to less than the 85th percentile is considered to be normal/healthy.

^bAmplitude was 4 times greater than on the right side.

Results

Patients were treated from February 18, 2010, through April 15, 2014. A total of 7 patients (5 female and 2 male; age range, 8-49 years) from 3 families underwent evaluation.

Family A

During a 9-month period, 3 adult first-degree relatives presented to our department for dizziness or aural fullness. Patient A-1 reported episodic disequilibrium that had been present for over 15 years. The disequilibrium was exacerbated by straining. She had bilateral aural fullness, which was worse in the left ear. The left ear was also sensitive to loud sounds and had pulsatile tinnitus. Her medical history was positive for migraine. On examination, her BMI was 20.4. Results of otomicroscopy were normal bilaterally. Hennebert sign and Tullio phenomenon were present only in her left ear. Her audiogram showed normal hearing in the right ear and supranormal bone conduction thresholds with air-bone gaps of 10 to 30 dB in the left ear. The left ear demonstrated a reduced cervical VEMP threshold of 65 dB and elevated SP:AP ratio of 0.59. The right ear demonstrated a normal cervical VEMP and SP:AP ratio. A CT scan showed dehiscence of bone over the superior semicircular canal at the arcuate eminence bilaterally (Figure 1A-D). Tegmen dehiscence was also noted bilaterally. The patient was treated for migraine, but when symptoms did not improve, she elected to undergo left superior canal plugging via a middle cranial fossa approach. Dehiscence was confirmed intraoperatively, and she underwent successful plugging of the left superior semicircular canal. Immediately after the surgery, the patient complained of hearing a clicking sound behind the right eye, which suggested that the procedure had unmasked symptoms in the right ear. She elected observation of this development, and the clicking sound improved after several months. She had resolution of her dizziness and all left ear symptoms. Results of testing obtained 3 months after the surgery showed normalization of the cervical VEMP and SP:AP ratio for the ear undergoing surgery.

Figure 1. Computed Tomographic Scan Findings for the 3 Patients in Family A.

Dehiscence of bone over the right superior semicircular canal (A, Stenver view; B, Poschle view) and the left superior semicircular canal were seen in patient A-1 (C, Stenver view; D, Poschle view). Dehiscence of bone over the superior semicircular canal at the arcuate eminence in the right ear was seen in patient A-2 (E, Stenver view; F Poschle view), and the bone over the left superior semicircular canal was thin over the lateral upslope of the canal (G, Stenver view; H, Poschle view). Bone over the superior semicircular canal of the right ear was very thin at the arcuate eminence in patient A-3 (I, Poschle view; J, Stenver view). Arrowheads indicate the superior semicircular canal.

Patient A-2 was seen several months later for bilateral aural fullness that had been present for 6 years. This symptom was associated with autophony and motion intolerance. She was sensitive to loud sounds but could not localize this to a particular ear. Her medical history was unremarkable. On examination, her BMI was 28.1. Results of otomicroscopy were normal bilaterally. A Hennebert sign was present in the right ear only. Her audiogram showed a mild conductive hearing loss with air-bone gaps of 5 to 15 dB in the right ear and borderline normal hearing in the left ear. Cervical VEMP thresholds were 65 dB bilaterally. The SP:AP ratios were 1.30 for the right ear (ie, the amplitude of the SP exceeded the amplitude of the AP, a phenomenon we have observed in a few cases of confirmed SCDS) and 0.80 for the left ear. A CT scan demonstrated dehiscence of bone over the right superior semicircular canal at the arcuate eminence (Figure 1E and F). The ipsilateral tegmen was dehiscent as well. The left ear had near dehiscence with thin bone at the lateral upslope of the superior semicircular canal (Figure 1G and H). She was diagnosed with right-sided SCDS and declined surgery.

Patient A-3 reported right aural fullness of unclear duration. Occasionally, loud sounds caused mild discomfort and mild disequilibrium. His medical history was unremarkable. On examination, his BMI was 26.9. Results of otomicroscopy were normal bilaterally. Tullio phenomenon and Hennebert sign were absent bilaterally. His audiogram showed a mild sensorineural loss at 2 kHz bilaterally with a small air-bone gap in the right ear. The right ear had a cervical VEMP threshold of 65 dB and SP:AP ratio of 0.68. The cervical VEMP and SP:AP ratio were normal for the left ear. A CT scan showed dehiscence of bone over the right superior semicircular canal at the arcuate eminence on only 1 Stenver view (Figure 1J). The tegmen was intact (Figure 1I). Left temporal bone structures were normal. The patient was diagnosed with near-dehiscence of the right superior semicircular canal. He was not offered surgical plugging given his mild symptoms.

Family B

Patient B-1 had bilateral sensorineural hearing loss and reported sensitivity to high-pitched sounds but could not localize this to a particular ear. His medical history was otherwise unremarkable. On examination, his BMI was 16.9, which is considered healthy and in the 70th percentile for his age and sex. Results of otomicroscopy were normal bilaterally. The patient’s audiogram showed a moderate to moderate-severe sensorineural hearing loss in a cookie-bite (ie, downsloping and then upsloping) configuration in both ears, but he also had a mild conductive overlay with air-bone gaps of 10 to 15 dB in the left ear. Temporal bone CT with only axial and coronal sequences revealed dehiscence of the bone over the left superior semicircular canal (Figure 2A and B). On coronal sequences, this dehiscence appeared to be located at the arcuate eminence with no obvious defect of the tegmen. Cervical VEMP thresholds were present at 80 dB bilaterally, but the amplitude of the response in his left ear was 4 times as large as that in the right ear. Electrocochleography was not performed because it is not routinely offered to pediatric patients at our institution. He was diagnosed with left-sided SCDS, and observation was recommended given his nondisabling symptoms.

Figure 2. Computed Tomographic Scan Findings for the 2 Patients in Family B.

Dehiscence of bone over the left superior semicircular canal at the arcuate eminence as seen on 2 coronal images of patient B-1 (A and B). Patient B-2 had dehiscence of the superior semicircular canal (C, Stenver view; D, Poschle view) and tegmen in the right ear (E). There was radiographic dehiscence at the arcuate eminence in the left ear (F, Stenver view; G, Poschle view). Arrowheads indicate the dehiscence.

Patient B-2 reported having many SCDS-related symptoms that dated back almost 20 years. These symptoms included exquisite sensitivity to sounds in her left ear. On examination, her BMI was 27.2. Results of otomicroscopy were normal bilaterally. Hennebert sign was absent bilaterally, but she had a marked Tullio phenomenon in her left ear. An audiogram showed a mild low-frequency conductive hearing loss with air-bone gaps of 25 to 40 dB and a supranormal bone conduction threshold in the left ear. Temporal bone CT showed dehiscence at the arcuate eminence bilaterally (Figure 2C-G). The tegmen was also dehiscent bilaterally. The left ear had a cervical VEMP threshold of 65 to 70 dB and SP:AP ratios ranging from 0.42 to 0.63. The right ear had a normal cervical VEMP and SP:AP ratios. The patient was diagnosed with SCDS in her left ear but declined surgery.

Family C

Patient C-1 reported autophony along with aural fullness and pulsatile tinnitus in the left ear. She experienced episodic disequilibrium triggered by blowing her nose or with rapid movements. Her medical history was notable for migraine, hypertension, and gastroesophageal reflux disease. On physical examination, her BMI was 39.1. Results of otomicroscopy were normal bilaterally. Hennebert sign and Tullio phenomenon were absent bilaterally. An audiogram revealed essentially normal hearing bilaterally except for several small air-bone gaps in the left ear with a supranormal bone conduction threshold. A CT scan revealed dehiscence of bone over the left superior semicircular canal at the arcuate eminence (Figure 3A and B). An ipsilateral tegmental defect was found with soft tissue opacification in the middle ear with ossicular contact. Right temporal bone structures were normal. The left ear had a low cervical VEMP threshold of 65 dB and an elevated SP:AP ratio of 0.72. The cervical VEMP threshold and SP:AP ratio in the right ear were normal. The patient was diagnosed with left-sided SCDS but declined surgical treatment.

Figure 3. Computed Tomographic Scan Findings for the 2 Patients in Family C.

Dehiscence of bone at the arcuate eminence (A, Stenver view; B, Poschle view) and the tegmen of the left ear was seen in patient C-1 (C; arrowhead indicates dehiscence). Dehiscence of bone over the right superior semicircular canal was seen in patient C-2 (D, Stenver view; E, Poschle view). Arrowheads indicate the superior semicircular canal.

Patient C-2 denied any dizziness or auditory symptoms. Her medical history was significant for hypertension, migraine, and gastroesophageal reflux disease. On physical examination, her BMI was 30.3. Results of otomicroscopy were normal bilaterally. Hennebert sign and Tullio phenomenon were absent bilaterally. An audiogram revealed essentially normal hearing with small air-bone gaps bilaterally. On temporal bone CT, the right ear had a small dehiscence over the superior semicircular canal at the arcuate eminence, but the tegmen was intact (Figure 3D and E). Bone over the left superior semicircular canal and ipsilateral tegmen was intact. The SP:AP ratios and cervical VEMP thresholds were abnormal bilaterally. The patient was diagnosed with right-sided SCDS and elected to undergo observation.

Zygosity Testing

Patients C-1 and C-2 consented to zygosity testing to determine the nature of their twin relationship. A blood sample was obtained from each patient and sent to a commercial laboratory for zygosity testing (Mayo Medical Laboratories, Rochester, Minnesota). Zygosity testing involved analysis of the following 12 polymorphic markers: D2S2368, D6S441, D7S484, D8S262, D10S197, D13S158, D14S70, D15S1002, D16S520, D17S250, D21S1252, and mycl. The genotypes for the tested markers were the same for patients C-1 and C-2, which strongly suggests monozygosity.

Discussion

Most cases of SCDS are single and sporadic, without an obvious cause for the dehiscence. Disagreement continues as to whether the dehiscence represents a congenital or an acquired anomaly. A congenital defect in ossification is supported by the results of a temporal bone survey and the presence of radiographic dehiscence in young children. A defect in ossification of the superior semicircular canal seems to be more plausible than arrested development given that the horizontal semicircular canal ossifies last and is rarely found to be dehiscent in the absence of cholesteatoma.

One study linked obesity and obstructive sleep apnea to the presence of radiographic dehiscence. Regarding obesity, Schutt et al reported that the mean BMIs of patients with and without radiographic dehiscence were 31.62 and 28.01, respectively. In our series, 2 of the 7 patients had BMIs in the healthy range, and 3 had BMIs in the mild overweight range.

Familial SCDS is rare. A total of 5 families have been described in the literature to date, and all involved 2 adult first-degree relatives. El Hadi et al described twin sisters with SCDS and coexisting tegmen defect but never established whether the twins were monozygotic or dizygotic. Niesten et al suggested that the occurrence of SCDS among relatives implicates a genetic basis; however, none of their familial cases of SCDS include information on BMI, which is potentially a confounding variable.

We believe that by contributing these 3 families with SCDS, we strengthen the case for a possible molecular genetic basis for the condition in some affected individuals. This series can be differentiated from prior reports of familial SCDS because it (1) includes BMI data and establishes that relatives with healthy weight can be affected, which argues against obesity as a contributing factor; (2) provides the first documentation of occurrence in a pediatric first-degree relative; and (3) establishes its occurrence in monozygotic twins. None of the patients discussed herein has a known history of obstructive sleep apnea, a disorder of bone metabolism, or intracranial hypertension. We acknowledge that we did not have polysomnography data to formally exclude obstructive sleep apnea.

Prior attempts at finding a genetic basis for SCDS have only involved searching for a few specific genes among sporadic cases. Characterization of familial cases of SCDS will be essential to identifying a gene or genes that underlie this disorder. A segregation analysis would allow for testing of best-fit models for pattern of inheritance but would require a large number of affected pedigree member pairs. For example, the seminal segregation analysis for otosclerosis was based on 150 sibships. The number of families required to identify genes would depend on the number of genes involved and would likely require collaboration among otolaryngologists at several institutions. If identification of a molecular genetic basis for SCDS is ultimately successful, similar techniques could be used in patients with other sites of otic capsule dehiscence to determine whether these disorders are distinct or part of a continuum.

Strengths and Limitations

This study is limited by its retrospective nature and small numbers. The strengths of our study include the fact it is the most detailed assessment of familial SCDS cases to date.

Conclusions

We believe our findings lend additional support to a developmental etiology. Our findings raise the prospect of a molecular genetic basis for this condition. Symptomatic first-degree relatives of patients diagnosed with SCDS should be offered evaluation to improve detection of this disorder.