HRCT and MRI findings in X-linked non-syndromic deafness patients with a POU3F4 mutation

doi:10.1016/j.ijporl.2014.08.013

International Journal of Pediatric Otorhinolaryngology

Volume 78, Issue 10, October 2014, Pages 1756-1762

https://doi.org/10.1016/j.ijporl.2014.08.013 Get rights and content

Abstract

Objective

The aim of this study was to analyze HRCT and MRI findings in patients with X-linked non-syndromic deafness and a POU3f4 mutation.

Methods

HRCT and MRI data of four patients (males, 2–19 years old) with a POU3f4 mutation were collected and a retrospective review was performed. Cochlea, internal auditory canal (IAC), vestibule, semicircular canals, vestibular aqueduct, nerve canals in the IAC fundus, stapes and cochlear nerve were evaluated on 2D images (multi-planner reformation, MPR) and cochlear foramen on 3D images (CT virtual endoscopy, CTVE). Ten cases with normal hearing subjected to CT and MR exams served as controls.

Results

Inner ear malformations were bilateral and symmetrical. Cochlear malformation was shown to consist of as a relatively normal outer coat shape, absence of a cochlear modilous, and a direct intercommunication between the IAC and cochlear inner cavity. The lateral portion of the IAC was dilated. A spiral cochlear inner cavity was observed with CTVE images versus a helical cochlear nerve foramen as seen in controls. The labyrinthine facial nerve canal and superior vestibular nerve canal were enlarged. The Bill's bar was hypertrophic and partially pneumatized. A thickened stapes footplate was present and a fissura ante fenestram was absent in seven ears examined. A column shaped stapes was observed in one ear.

Conclusions

The absence of a cochlear modilous with a dilated lateral IAC and thickened stapes footplate were the remarkable features observed with imaging these in X-linked non-syndromic deafness patients with a POU3F4 mutation. Preoperative recognition of the image features in these patients is important because it precludes stapedectomy and indicates the risks in the surgery of cochlear implantation including CSF gusher and electrode insertion into IAC.

Introduction

Currently, high resolution computed tomography (HRCT) remains the modality of choice for assessing congenital inner ear malformations. Helical multi-detector scanners not only provide a means for rapid imaging but also have the capacity to reconstruct inner and middle ear structures in any 2D plane or 3D images. Although bony structures of the inner and middle ear can be effectively displayed on HRCT images, the membranous labyrinth and the nerves of the internal auditory canal (IAC) can only be evaluated with magnetic resonance imaging (MRI). Accordingly, HRCT and MRI are often used as complementary approaches in the study of inner ear malformations [1].

It has been established that X-linked deafness is clinically and genetically a heterogeneous disease accounting for less than 2% of non-syndromic hearing loss. Two genes, PRPS1 (responsible for DFNX1) and POU3F4 (responsible for DFNX2), have been identified as contributing to this form of hearing impairment. Deafness caused by POU3F4 mutation accounts for 50% of all cases of X-linked non-syndromic hearing loss [2], [3]. Inner ear malformations as specifically caused by POU3F4 mutation have only been reported in a few sporadic cases [2], [4], [5]. Most studies on non-syndromic hearing loss have focused on gene analysis, while data from imaging have rarely been incorporated within these studies. The purpose of this retrospective study is to present the HRCT and MRI findings of four patients with X-linked non-syndromic deafness possessing a POU3F4 mutation.

Section snippets

Study population

The institutional research ethics review board approved this retrospective study. HRCT and MRI data from four patients with a POU3F4 mutation were collected at our institute from July 2004 to September 2013. All patients were male and ranged in age from 2 to 19 years. Two of the cases with congenital sensorineural hearing impairment were from the same family, while the other two cases with congenital mixed hearing impairment were from different families. Gene diagnoses of all patients were

Results

All inner ear malformations were bilateral and symmetrical within each of the four cases. Stapes abnormalities in two patients were not symmetrical.

Discussion

HRCT or MRI is often used as an initial screening tool in the examination of patients with congenital hearing loss. However, middle and inner ear structures are not optimally depicted with HRCT or MRI as oriented in conventional axial, coronal or sagittal planes due to their sloping position. For example, the stapes appears as a tiny round and strip structure, which distorts its true shape [6]. Recent advances in multi-detector CT and some scanning sequences of MRI, allow the acquisition of

Conclusions

In this study, bilateral symmetrical inner ear malformations (including absent of cochlear modilous, dilated lateral IAC) and thickened stapes footplate are the remarkable imaging features in X-linked non-syndromic deafness patients with a POU3F4 mutation. Genetic counseling should be included when the similar image findings are found in patients with congenital hearing impairment. Recognition of the imaging features in these patients is important because it changes the treatment and precludes

References (17)

J.W. Casselman et al.
CT and MR imaging of congenital abnormalities of the inner ear and internal auditory canal
Eur. J. Radiol.
(2001)
J. Li et al.
Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese family with X-linked nonsyndromic hearing loss
J. Genet. Genomics
(2010)
T. Nakasato et al.
Virtual CT endoscopy of ossicles in the middle ear
Clin. Imaging
(2001)
Y.J. de Kok et al.
Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4
Science
(1995)
A.P. Vore et al.
Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness
Arch. Otolaryngol. Head Neck Surg.
(2005)
Q.J. Wang et al.
A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family
Laryngoscope
(2006)
P. Henrot et al.
Current multiplanar imaging of the stapes
Am. J. Neuroradiol.
(2005)
J.I. Lane et al.
Middle and inner ear: improved depiction with multiplanar reconstruction of volumetric CT data
Radiographics
(2006)

There are more references available in the full text version of this article.

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A detailed search of electronic databases has been conducted, including PubMed, Ovid Medline, Scopus, Cochrane Library, Google Scholar, National Institute for Health and Care Excellence (NICE), Embase, and PsycINFO.
Syndromic causes of hearing loss are characterised by different and sometimes specific abnormalities in the temporal bone.
A complete knowledge of the image findings in the temporal bones, brain, skull and other body regions is critical for the optimal assessment and management of these patients.
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Early identification of this defect may impact patient family counseling and influence options for hearing rehabilitation. Preoperative CT may be interpreted as “normal” by a neuroradiologist, however, features such as a bulbous or dilated IAC, modiolar anomalies, and abnormal vestibular aqueducts must be identified due to their associated with X-linked hearing loss, the POU3F4 mutation, and congenital stapes fixation [9,22–24]. These features are typically visible on axial or coronal CT images, whereas cochlear basal turn patency is best appreciated on oblique and parasagittal reformations of a high resolution scan.
Perilymph gusher (PLG), an uncommon complication of otologic surgery, has been attributed to communication between the cochlea and the internal auditory canal (IAC). Subtle osseous defects may be missed on routine review of computed tomography (CT). This study aimed to quantify cochlear basal turn patency not seen on axial CT in patients with PLG and compare those against patients without intraoperative PLG.
Ears that underwent cochlear implantation or stapedotomy with preoperative helical CT that was interpreted as “normal” at a tertiary referral center. An otologist and a radiologist independently and in a blinded fashion measured the dimensions of cochlear basal turn patency on CT images in oblique plane and parasagittal planes along the interface of the cochlea and IAC fundus.
Sixty-one ears were reviewed, including 3 with surgically confirmed PLGs and 12 with apparent dehiscence without a PLG. Mean defect width with PLG was 0.83 mm (range 0.75–0.9 mm) and without PLG was 0.43 mm (range 0.3–0.65 mm, p = 0.011). A greater proportion of PLGs occurred in ears with defects (3 of 15) than in ears without (0 of 46, p = 0.013). Using a cutoff of 0.75 mm, a greater proportion of PLGs occurred with defect width >0.75 mm (3 of 3) than in defects <0.75 mm (0 of 12, p = 0.022).
CT dehiscence between the IAC and cochlear basal turn, particularly with a width > 0.75 mm, should be considered a risk for PLG with stapedotomy or cochlear implantation.
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The comprehensive clinical examination of both half-brothers revealed the association of novel truncating transition c.975G>A (p.Trp325*) in the POU3F4 gene with inner ear malformations (“corkscrew” cochlea with an absence of modiolus) and mixed (sensorineural and conductive) progressive bilateral hearing loss. These clinical features correspond to early reported cases of the male patients with hemizygous pathogenic variants in the POU3F4 gene associated with DFNX2 [16–30]. Moreover, the enlargement of semicircular canals and the postural disorders manifesting as a moderate vertical instability according to the Romberg test (Appendix B. Supplementary Fig. 2C) were detected by additional MRI and computed stabilometry in two affected siblings with c.975G>A (p.Trp325*) in the POU3F4 gene.
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View full text

HRCT and MRI findings in X-linked non-syndromic deafness patients with a POU3F4 mutation

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Conclusions

Eur. J. Radiol.

J. Genet. Genomics

Clin. Imaging

Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4

Science

Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness

Arch. Otolaryngol. Head Neck Surg.

A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family

Laryngoscope

Current multiplanar imaging of the stapes

Am. J. Neuroradiol.

Middle and inner ear: improved depiction with multiplanar reconstruction of volumetric CT data

Radiographics