Volume 3, Issue 4 , Pages 177-181, December 2008
Head trauma as eliciting event in transient deterioration of sensorineural hearing loss and vertigo in Pendred/EVA syndrome
Article Outline
- Summary
- 1. Introduction
- 2. Report of a case
- 3. Discussion
- Conflict of interest statement
- References
- Copyright
Summary
A patient with Pendred/enlarge vestibular aqueduct (EVA) syndrome with a 26-year audiometric follow-up is presented, showing childhood onset of sensorineural hearing loss, characterized by several episodes of well-documented sudden transient deterioration in sensorineural hearing loss and vertigo elicited by head trauma. This report is unique in its detailed follow-up of hearing loss around the time of head trauma events, providing new evidence to show a causative relation between head trauma and sudden hearing loss in EVA/Pendred syndrome.
Keywords: Pendred syndrome, SLC26A4 gene, Enlarged vestibular aqueduct (EVA), Head trauma, Sensorineural hearing loss, Vertigo
1. Introduction
Pendred/enlarge vestibular aqueduct (EVA) syndrome is an autosomal recessive hereditary disorder, characterized by the childhood onset of sensorineural hearing loss and goitre. This syndrome might account for 4.3–7.5% of all cases of congenital childhood deafness [1].
Since 1997, it is known that Pendred syndrome is caused by mutations in the SLC26A4 gene on the long arm of chromosome 7 that encodes a transmembrane protein called pendrin [2]. It was found that mutations in SLC26A4 also cause EVA syndrome [3].
Thyrocyte function was found to be impaired by the detriment of iodide–chloride transport [4]. Due to a partial defect in the organification of iodide, the perchlorate test is usually positive. In approximately 80% of patients with Pendred syndrome, goiter had developed by a mean age of 8 years [5].
In a pathological study on the inner ear of mice, the Pendred's syndrome gene mouse ortholog was localized in the endolymphatic duct and sac [6], where it is very likely to be involved in the regulation of endolymph composition as a transmembrane anion transporter. SLC26A4 knockout-mice developed severe dilatation of the endolymphatic sac and duct from day 15 of embryonic development [7].
The vestibular aqueduct might have an important role in minimizing changes in intracranial pressure. It is possible that intracranial pressure increases are advanced more strongly into the inner ear due to the widened vestibular aqueduct. During a shockwave, endolymph might flow from the endolymphatic sac through the vestibular aqueduct into the vestibule. There is a difference in ion composition between the fluid in the endolymphatic sac and the fluid in the cochlea. The influx of fluid from the endolymphatic sack may disturb the action potential in the cochlea. This might possibly cause a transient endolymphatic hydrops or ruptures of the round window membrane or Reisner's membrane. This could explain why hearing loss seems to be aggravated by head trauma in patients with Pendred/EVA syndrome, as previously described by Jackler et al. [8] and Colvin et al. [9]. We present a patient with Pendred syndrome who showed an especially clear pattern of sudden transient increases in sensorineural hearing loss and vertigo after well-defined head trauma.
2. Report of a case
Our patient was a 29-year-old woman when she was referred to our tertiary hospital. She had no sibs and there was no known consanguinity or positive family history of hearing impairment. Pregnancy and delivery had been uneventful. At the age of 5 years, her audiogram was found to be abnormal and regular subsequent audiograms showed progressive sensorineural hearing loss (Fig. 1A). Otoscopy did not show any abnormalities. From the age of 5 years, she started to wear bilateral hearing aids. Goitre was observed at 16 years of age, which ultimately led to total thyroidectomy at the age of 20 years, followed by thyroxine replacement therapy.
Fig. 1.
Course of the hearing loss over time: (A) shows mean hearing loss (0.5, 1 and 2
kHz) in both ears; “E” marks an event of head trauma followed by transient profound hearing loss; (B) shows audiometry results in both ears at different ages.
Hearing loss was slowly progressive, but variable in intensity. Her right ear had always been her best ear. At the age of 11 years, the mean level of hearing impairment (0.5, 1 and 2kHz) was 30dB in the right ear and 70dB in the left ear (Fig. 1B). In the right ear, her speech discrimination score was 100% at 90dB.
There were episodes of deterioration in hearing loss accompanied by vertigo and imbalance, accompanied by nausea and vomiting. Each time these were followed by recuperation. She had suffered four short periods of profound deafness. The first time, at 12 years of age, the episode with vertigo had lasted only a few days. She herself nor her parents are currently able to describe the sensation of vertigo during the first and second episode. The second episode (age 20 years) lasted 4 weeks. Afterwards, the mean hearing level (PTA0.5,1,2kHz) in her right ear was 87dB at first and around 60dB in the following period, while her left ear was profoundly deaf. Maximum speech recognition score was 60%. It was not clear whether these first two episodes had been provoked by head trauma, although she had been very active in ball sports at that time.
At the age of 29 years, the gaff of a sailing boat had struck her head during a sailing trip and she had again become profoundly deaf for 7 days. She suffered from vertigo, nausea and vomiting. Afterwards, her hearing returned to the same levels as those prior to the incident. In the right ear, the PTA0.5,1,2kHz was 57dB and her speech discrimination score was 100% at 70dB. Her left ear remained profoundly deaf.
In the same year, computed tomography (CT) scanning and magnetic resonance imaging (MRI) were performed on the petrous bones (Fig. 2A and B). These showed bilateral widened vestibular aqueducts. The left was wider than the right, which was in accordance with the more severe hearing loss on that side. On the left, the vestibular aqueduct had the same diameter as the internal acoustic canal and the endolymphatic sac was distinctly enlarged. On the right, the diameter of the vestibular aqueduct was slightly larger than a semicircular canal. Mutation analysis identified a homozygous missense mutation c.707C>T (p.Leu236Pro) in SLC26A4. This mutation is fairly common in patients with Pendred syndrome. Mutation analysis in the parents was not performed. Since the patient had a homozygous mutation, it can be expected that both parents were carrier of this mutation. Electronystagmography showed discrepancies in labyrinthine function in favor of the right vestibulum.
Fig. 2.
(A) High-resolution CT scan of the temporal bone. Axial slice at the level of the vestibule. Enlarged vestibular aqueducts: 2.5
mm on the right side and 3.4 on the left (arrows). 1.5mm is normal, measured midway along the duct; (B) shows high-resolution T2-weighted MR images of the skull base. Vestibular ducts and sacs are enlarged on both sides (arrows).
Recently, the patient experienced her fourth temporary setback in hearing with paroxysmal vertigo and tinnitus after accidentally striking her head on the lectern of a pipe organ. She has been advised to be very careful regarding head trauma and barotrauma. Fig. 1A and B show the course of the hearing loss over time.
3. Discussion
The diagnosis in this patient should be Pendred syndrome, although the opportunity to perform a perchlorate test in time was not used, since that diagnosis was not considered prior to the thyroidectomy. The hotspot mutation reported confirms the diagnosis EVA/Pendred syndrome. All patients with Pendred syndrome have EVAs. In one of our previous studies [5], all seven patients with Pendred syndrome who underwent CT scanning or MRI had EVAs and four had additional hypoplasia of the cochlea. Phelps et al. [10] examined 20 Pendred patients using MRI and found that all of them had EVA. The EVA syndrome is also caused by mutations in SLC26A4 [11]. Patients with the EVA syndrome suffer from fluctuating, progressive, moderate to severe sensorineural hearing loss and disequilibrium symptoms [12]. Goitre and/or thyroid dysfunction occur in about 80% of patients with Pendred syndrome, thus the two syndromes are slightly different clinical entities based on the same pathological process.
The clinical presentation of patients with mutations in SLC26A4 is variable. Features range from nonsyndromic autosomal recessive sensorineural hearing impairment with enlarged vestibular aqueducts (DFNB4) to classical Pendred syndrome (profound childhood deafness and the development of goitre in adolescence or early childhood). Hearing loss in patients with two mutant alleles in SLC26A4 is more severe than in patients with no or one mutant allele [13], [14]. Currently, it is not clear whether certain mutations cause specific inner ear pathology. Future research into genotype-phenotype correlation in the most common SLC26A4 mutations (hotspot mutations) could help to match clinical and pathological features to particular mutations.
It is reported to be typical for hearing impairment to fluctuate and progress over time in patients with enlarged vestibular aqueducts. This pattern was also observed in our patient. Well-defined head trauma elicited episodes of well-documented transient deterioration in sensorineural hearing loss and vertigo. Such a detailed report is quite unique and substantiates this causative relation, which until now usually is only based on data from the patient's medical history. Such observations in patients with EVAs, based on the medical history, were previously made by Colvin et al. [9] in 2006 and Jackler et al. [8] in 1989. The pattern of hearing loss was described as progressive and stepwise, often triggered by relatively minor head trauma [8]. It is possible that the (transient) deterioration in hearing loss and vertigo after head trauma can be explained by a sudden increment in intracranial pressure that is passed on to the vestibulum via the enlarged vestibular aqueduct. The exact pathological process in the inner ear evoked by this process is not yet elucidated. In our patient, the left vestibular aqueduct was larger than the right, corresponding with a more severe hearing loss in the left ear. Yet in a study by Colvin et al., a correlation between the size of the endolymphatic sac or diameter of the vestibular aqueduct and the deterioration in hearing loss following head trauma could not be established [9].
When children present with sudden progression of sensorineural hearing loss, images of the inner ear should be obtained. It is also worthwhile to consider the possibility of vestibular aqueduct enlargement in the case of transient post-traumatic hearing loss. Patients with widened vestibular aqueducts should be advised to avoid head trauma. This can be achieved with extra precautionary measures during sport and other activities and recommendations about lifestyle and choice of work. To confirm the clinical diagnosis, mutation analysis can be performed on the SLC26A4 gene.
Conflict of interest statement
All authors do not have any financial or personal relationships with other people or organizations that could inappropriately influence (bias) this report. This study is not sponsored.
References
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PII: S1871-4048(08)00027-0
doi:10.1016/j.pedex.2008.03.007
© 2008 Published by Elsevier Inc.
Volume 3, Issue 4 , Pages 177-181, December 2008
