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The Laryngoscope
Lippincott Williams & Wilkins
© 2007 The American Laryngological,
Rhinological and Otological Society, Inc.
Otopathology in Mohr-Tranebjærg Syndrome
Fayez Bahmad, Jr, MD; Saumil N. Merchant, MD; Joseph B. Nadol, Jr, MD;
Lisbeth Tranebjærg, MD, PhD
Background: Mohr-Tranebjærg syndrome (MTS)
is an X-linked, recessive, syndromic sensorineural hear-
ing loss (HL) characterized by onset of deafness in child-
hood followed later in adult life by progressive neural
degeneration affecting the brain and optic nerves. MTS is
caused by mutations in the DDP/TIMM8A gene, which
encodes for a 97 amino acid polypeptide; this polypeptide
is a translocase of the inner mitochondrial membrane.
Objectives: To describe the otologic presentation
and temporal bone histopathology in four affected indi-
viduals with MTS.
Material and Methods: All four subjects be-
longed to a large, multigenerational Norwegian fam-
ily and were known to carry a frame shift mutation in
the TIMM8A gene. Temporal bones were removed at
autopsy and studied by light microscopy. Cytoco-
chleograms were constructed for hair cells, stria vas-
cularis, and cochlear neuronal cells. Vestibular neu-
rons were also counted.
Results: All four subjects developed progressive HL
in early childhood, becoming profoundly deaf by the age of
10 years. All four developed language, and at least one
subject used amplification in early life. Audiometric eval-
uation in two subjects showed 80- to 100-dB HL by the
age of 10 years. The subjects died between the ages of 49
and 67. The otopathology was strikingly similar in that
all bones examined showed near-total loss of cochlear
neuronal cells and severe loss of vestibular neurons.
When compared with age-matched controls, there was
90% to 95% loss of cochlear neurons and 75% to 85% loss
of vestibular neurons.
Conclusions: We infer that the HL in MTS is likely
to be the result of a postnatal and progressive degenera-
tion of cochlear neurons and that MTS constitutes a true
auditory neuropathy. Our findings have implications for
clinical diagnosis of patients with MTS and management
of the HL.
Key Words: Temporal bone, histopathology, heredi-
tary hearing loss, Mohr-Tranebjærg syndrome.
Laryngoscope, 117:1202–1208, 2007
INTRODUCTION
Mohr-Tranebjærg syndrome (MTS) is an X-linked,
recessive, syndromic hearing loss (HL) characterized by
deafness in childhood and followed later in life by progres-
sive neural degeneration affecting the brain and optic
nerves.
1–3
The typical initial manifestation is a progressive
sensorineural HL (SNHL) in childhood, with profound HL
usually occurring by the age of 10 years. Other features of
the syndrome become evident later in life, including pro-
gressive visual loss leading to blindness, dystonia, spas-
ticity, aggressive behavior, paranoia, dysphagia, and
dementia.
MTS is caused by mutations in a gene on Xq22 that
was initially named “DDP” for deafness/dystonia peptide.
4
The gene encodes a small polypeptide containing 97 amino
acids. Investigations using yeast cells showed that DDP is
a mitochondrial protein and is part of a transport complex
that mediates protein transport.
5
Mutations in the gene
are believed to result in a defect in mitochondrial protein
import, leading to defects in mitochondrial function. The
DDP gene was renamed TIMM8A to reflect the function of
its encoded polypeptide, which is a translocase of the inner
mitochondrial membrane.
Examination of the temporal bone from an affected
individual with MTS showed loss of ganglion cells within
the cochlear and vestibular nerves.
6
Since that report, we
have had the opportunity to study the temporal bones
from three additional affected individuals with MTS. We
describe our findings in all four subjects in the present
study.
MATERIALS AND METHODS
All subjects of this report belong to a large, multigenera-
tional Norwegian family with 16 affected members.
3
All affected
individuals are male. The four subjects that we studied are des-
ignated V:3, V:16, V:17, and VI:24 in the pedigree shown in
Figure 1. All four individuals had been shown to carry a frame
shift mutation characterized by a 1 base pair deletion of T at
nucleotide position 151 in axon 1 of the TIMM8A gene, 151delT
From the Department of Otolaryngology (F.B., S.N.M., J.B.N.), Massa-
chusetts Eye and Ear Infirmary, Boston, Massachusetts, U.S.A.; the De-
partment of Otology and Laryngology (F.B., S.N.M., J.B.N.), Harvard Medical
School, Boston, Massachusetts, U.S.A.; the Department of Audiology (L.T.),
Bispebjerg Hospital, Wilhelm Johannsen Centre of Functional Genomics,
Institute for Molecular and Cellular Medicine, The Panum Institute,
Copenhagen, Denmark; and the Department of Medical Genetics, Univer-
sity Hospital, N-Tromsø, Norway.
Editor’s Note: This Manuscript was accepted for publication March
6, 2007.
Supported in part by NIH grant 1U24DC008559 (S.N.M.) and by
grants (L.T.) from the Oticon Foundation, Denmark.
Send correspondence to Dr. Saumil N. Merchant, Massachusetts Eye
and Ear Infirmary, 243 Charles Street, Boston, MA 02114-3096. E-mail:
saumil_merchant@meei.harvard.edu
DOI: 10.1097/MLG.0b013e3180581944
Laryngoscope 117: July 2007 Bahmad et al.: Otopathology in Mohr-Tranebjærg Syndrome
1202
(Q38fsX64). According to revised terminology, the mutation is
now called 116delT (Q38fsX64).
Temporal bones were removed at autopsy and processed for
light microscopy in the standard manner, including fixation using
10% neutral buffered formalin, decalcification using ethylenedia-
minetetraacetate, embedment in celloidin, serial sectioning in the
axial plane at a thickness of 20
m, and hematoxylin and eosin
staining of every 10th section.
7
All stained sections were exam-
ined by light microscopy. Graphic reconstruction of the cochlea
was performed according to the method described by Schuknecht
7
to determine loss of various neurosensory elements such as hair
cells, stria vascularis, and cochlear neuronal cells. Cochlear neu-
ronal cell counts were compared with normative data reported by
Schuknecht.
7
Counts of vestibular neurons (Scarpa’s ganglion)
were also performed using the method described by Richter
8
and
compared with normative data reported by Vela´zquez et al.
9
RESULTS
Case V:16, History
This case was previously reported,
6
and, therefore,
only a brief description is provided. This patient was
known to be “deaf” from approximately the age of 4 years.
He developed language and enjoyed singing. He started to
lose vision at age 48 and developed typical neurologic
symptoms of dystonia and dysphagia in his late 50s. He
died at age 67 from pneumonia, and the right temporal
bone was removed at 29.5 hours postmortem.
Histopathology
Figure 2A shows the cytocochleogram. The inner ear
shows near-total loss of cochlear neurons. When compared
with normative data from age-matched controls, 92% of
the neurons are missing. The total cochlear neuronal
count is 1,765. Except for some slight losses in the apical
turn, other structures within the cochlea are preserved,
including outer and inner hair cells and supporting cells of
the organ of Corti, stria vascularis, tectorial membrane,
spiral limbus, and the spiral ligament. Within the vestib-
ular system, there is a severe loss of vestibular ganglion
cells (total count, 4,638, which is a 76% loss compared
with age-matched controls). The sensory and supporting
cells of the vestibular sense organs and the vestibular
membranous labyrinth appear normal. Cells of the genic-
ulate ganglion of the facial nerve appear healthy and are
present in normal numbers. The specimen also contains a
part of the trigeminal ganglion, whose neurons are
present in normal numbers. The external and middle ears
as well as the mastoid and otic capsule appear normal.
Case V:3, History
This patient developed HL around the age of 3 years
and was known to be “deaf” from approximately the age of
7. He developed some language and attended a school for
the deaf. No formal audiometric studies were performed.
He had normal mental function in early life with good
social skills. He developed the typical features of the MTS
syndrome later in adult life including spasticity, dystonia,
aggressive behavior, paranoia, and dementia. He had
ataxia of hand movements and of gait as well as photo-
phobia and visual loss. He suffered from a fracture of the
femur at age 51. His terminal illness was precipitated by
a bout of esophagitis leading to bloody vomiting and pro-
gressive deterioration of his general health. He died at the
age of 63. The cause of death is not known. His body was
refrigerated until autopsy was performed at 72 hours post-
mortem. The left ear is available for study.
Histopathology
There is a large, central perforation of the tympanic
membrane along with tympanosclerosis and thickening of
the pars propria of the surrounding drum remnant. The
submucosa of the middle ear and mastoid is thickened and
infiltrated with lymphocytes and round cells. There are
fibrocystic changes involving the round window niche and
parts of the epitympanum, mesotympanum, and mastoid.
The ossicles show small areas of resorption of bone sur-
rounding vascular spaces, but the ossicular chain is in
Fig. 1. Pedigree of large, multigenerational, Norwegian family with Mohr-Tranebjærg syndrome. There are 16 affected members, all male.
Subjects V:3, V:16, V:17, and VI:24 are the focus of this report and are marked by circles.
Laryngoscope 117: July 2007 Bahmad et al.: Otopathology in Mohr-Tranebjærg Syndrome
1203
continuity. The otic capsule appears normal. These changes
in the middle ear and mastoid are consistent with a diag-
nosis of inactive chronic otitis media.
A cytocochleogram of the ear is shown in Figure 2B,
and photomicrographs of the cochlea are shown in Figure
3. The most striking abnormality within the cochlea is
near-total loss of cochlear neurons in all turns, with severe
atrophy of both peripheral dendrites and central axons.
Both afferent and efferent nerve fibers are missing. The
total spiral ganglion count is 2,151, which represents a
91% loss compared with age-matched controls. The organ
of Corti including hair cells and supporting cells as well as
the stria vascularis are normal except in the apical 5 mm
where there is cystic degeneration of the stria vascularis
and partial loss of outer hair cells. Reissner’s membrane is
in normal position without endolymphatic hydrops. The
saccule, utricle, and all three semicircular canals show
normal appearing membranous walls, and their respec-
tive maculae and cristae show good populations of hair
cells and supporting cells. The vestibular nerve has been
partly avulsed from the internal auditory canal, but por-
tions that are present show moderate to severe loss of the
vestibular ganglion cells. The geniculate ganglion shows a
normal population of cells, although many of them are
pyknotic. The trigeminal ganglion appears normal.
Case VI:24, History
This subject was known to be “deaf” from approxi-
mately the age of 3 or 4 years. He developed language and
enjoyed singing. An audiogram at age 7 showed an 80- to
100-dB bilateral HL. He was fitted with hearing aids at
age 10 and attended a school for the deaf at age 12.
Another audiogram at age 21 also showed an 80- to 100-dB
bilateral HL. Electronystagmogram at age 21 was re-
ported to be normal. He developed the typical neurologic
symptoms of the MTS syndrome in his 20s and 30s, be-
ginning with an ataxic gait at age 25, followed by dystonia,
spasticity, involuntary movements, and hyperreflexia. He
developed photophobia at age 40 followed by progressive
visual loss. He had a foot fracture at age 33. He died from
pneumonia at age 49, and both temporal bones were re-
moved at 18.5 hours postmortem.
Histopathology
Many findings are similar between the two ears, and
the temporal bones are described together. There are also
a few differences between the two sides, as noted below.
The external auditory canal, middle ear, mastoid, and otic
capsule are normal on both sides. The cytocochleograms
are shown in Figure 2, C and D. There is near-total loss of
cochlear neuronal cells (total counts: right ear, 1,431, a
95% loss vs. age-matched counts; left ear, 2,826, a 90%
loss vs. age-matched). There is severe atrophy of the pe-
ripheral dendrites and central axonal processes of co-
chlear neuronal cells as well as loss of the intraganglionic
spiral bundle (efferent innervation). The organ of Corti
shows scattered loss of outer hair cells on the right,
whereas on the left, it is atrophic in the 0 to 20 mm region,
with loss of both outer and inner hair cells (Fig. 4). There
is mild atrophy of the stria vascularis in the left ear in all
turns. Both ears show apical endolymphatic hydrops, mild
atrophy of the spiral ligament in the more apical portions,
Fig. 2. Cytocochleograms of histologic
changes within the cochlea in the four
individuals in this report. Graphic recon-
struction of the cochlea was performed
in each ear according to the method
described by Schuknecht.
7
Missing or
abnormal elements (black). Vertical axes
of cytocochleogram boxes for the stria
and neurons show percentage of loss.
IHC ⫽inner hair cell; OHC ⫽outer hair
cell. Areas within hair cell histograms
marked by X represent regions where
cytologic evaluations could not be per-
formed. Note that the consistent feature
across all five temporal bones is near-
total loss of cochlear neurons. (A) Sub-
ject V:16, right ear. (B) Subject V:3, left
ear. (C) Subject VI:24, right ear. (D) Sub-
ject VI:24, left ear. (E) Subject V:17, right
ear.
Laryngoscope 117: July 2007 Bahmad et al.: Otopathology in Mohr-Tranebjærg Syndrome
1204
normal spiral limbus, and normal tectorial membrane.
The vestibular sense organs show good populations of hair
cells and supporting cells on both sides (Fig. 5). The ves-
tibular membranous labyrinth is normal on both sides.
The vestibular ganglion (of Scarpa) shows severe loss on
both sides (total counts: right, 3,669, an 82% loss vs.
age-matched controls; left, 4,346, a 78% loss vs. age-
matched). Geniculate ganglion cells are present in good
numbers on both sides. The left temporal bone shows a
part of the trigeminal ganglion, which appears to be nor-
mal. Blood vessels supplying the auditory and vestibular
sense organs are normal bilaterally. There is no inflam-
mation or deposition of new bone or fibrous tissue within
the inner ears.
Case V:17, History
This patient was known to be “deaf” from approxi-
mately the age of 3 years. He did develop language, and an
audiogram at age 13 showed a bilateral HL greater than
80 dB. He attended a boarding school for the deaf between
the ages of 10 and 15 years. He was noted to have no
intelligible speech at age 19. He was a fisherman and
continued this occupation until age 41 when he started to
lose vision. He was nearly completely blind by age 49 and
developed progressive neurologic symptoms in his 50s
characterized by dystonia, spasticity, contractures, and an
ataxic gait. He died at age 60 from bilateral bronchopneu-
monia, and the right temporal bone was removed 96 hours
after death.
Histopathology
The external auditory canal, middle ear, mastoid,
and otic capsule appear normal. A cytocochleogram of the
ear is shown in Figure 2E. There is near-total loss of
cochlear neurons, with loss of nearly all peripheral and
central axonal processes. The total cochlear neuronal
count is 1,485, which represents a 94% loss versus age-
matched controls. The atrophy includes loss of the intra-
ganglionic spiral bundle. Accurate assessments of the or-
gan of Corti cannot be made because of postmortem
autolysis, but it appears that hair cells are present. The
stria vascularis, spiral ligament, tectorial membrane, and
Fig. 3. Photomicrographs of cochlea from subject V:3. (A) Lower-power view showing cochlear turns and saccule. There is near-total loss of
spiral ganglion cells with severe atrophy of both peripheral and central axonal fibers. The saccule appears normal. The boxed area of the basal
turn is shown at higher magnification (B). Higher-power view of scala media from basal turn showing that the organ of Corti (including hair cells)
is intact. Other structures of the cochlear duct such as stria vascularis, spiral limbus, and tectorial membrane appear normal. Note absence
of nerve fibers in osseous spiral lamina. (C) High-power view of apical turn showing cystic degeneration of the stria vascularis and partial loss
of outer hair cells within the organ of Corti.
Laryngoscope 117: July 2007 Bahmad et al.: Otopathology in Mohr-Tranebjærg Syndrome
1205
spiral limbus appear normal. Reissner’s membrane shows
apical endolymphatic hydrops. The vestibular sense or-
gans show advanced autolysis, but it appears that hair
cells are present in the respective cristae and maculae.
There is severe loss of cells of Scarpa’s ganglion with
atrophy of the peripheral nerve fibers. The total Scarpa’s
ganglion count was 2,692, which represents an 85% loss
compared with age-matched controls. Blood vessels sup-
plying the auditory and vestibular end organs are present
without any evidence of vasculitis or occlusion. There is
also no deposition of connective tissue or new bone within
the inner ear. Cells of the geniculate and trigeminal gan-
glia are pyknotic but are present in normal numbers.
DISCUSSION
MTS is an X-linked syndrome characterized by pro-
gressive HL in childhood, followed later in life by progres-
sive neural degeneration affecting the brain and optic
nerves. There is phenotypic variability, both within and
between families affected with MTS.
1–3,10
The initial man-
ifestation of postlingual, progressive SNHL in the first
decade of life is shared by the majority of patients. How-
ever, congenital HL has also been reported.
11,12
Dystonia
is also a common clinical manifestation, but its onset is
more variable, ranging from the first to the fifth decade of
life.
2,3,10,12
Mild dystonia may be present in female carri-
ers who are heterozygous for TIMM8A mutations.
2,3,10,12
Although many different mutations in the TIMM8A gene
have been reported in families with MTS, it appears that
differences in the mutations cannot account for the phe-
notypic variability. The latter has been hypothesized to be
caused by modifier genes, environmental factors, or
both.
3,10
We examined five temporal bones from four individ-
uals belonging to the same family with MTS, all of whom
had an identical frame shift mutation in the TIMM8A
gene. All four subjects developed progressive HL in early
childhood, becoming profoundly deaf by the age of 10
years. All four developed language, and at least one sub-
ject used amplification in early life. Audiometric evalua-
tion in two subjects showed 80 to 100 dB threshold shifts
around the age of 10 years. All four developed neurode-
generation and vision loss that is typical of MTS later in
adult life and died between the ages of 49 and 67. There-
fore, all four subjects were profoundly hearing impaired
for a long period of time, between 40 and 60 years, de-
pending on the case.
The otopathology was strikingly similar in that all
bones examined showed near-total loss of cochlear neuro-
nal cells and severe loss of vestibular neurons. When
compared with age-matched controls, there was 90% to
95% loss of cochlear neurons and 75% to 85% loss of
vestibular neurons. It is also of note that the geniculate
and trigeminal ganglia were unaffected in all specimens
examined. The similarity of findings in these five temporal
bones reinforces the conclusion that was reached in our
earlier report based on examination of a single temporal
Fig. 4. Subject VI:24. Views of scala media from basal turn in right (A) and left (B) ears of subject. On left, the organ of Corti is missing, whereas,
it is intact and normal on right. Both sides show near-total loss of cochlear neurons and loss of nerve fibers in the osseous spiral lamina.
Fig. 5. Subject VI:24. Vestibular system showing normal appearance
of macula of utricle. There is loss of vestibular neuronal cells and
atrophy of vestibular nerve fibers.
Laryngoscope 117: July 2007 Bahmad et al.: Otopathology in Mohr-Tranebjærg Syndrome
1206
bone
6
that the otopathologic hallmark of MTS is a
severe neuropathy affecting the cochlear and vestibular
nerves. Thus, MTS constitutes a good example of a true
auditory neuropathy, of which there are few well-
documented examples in the literature with histopatho-
logic confirmation.
13,14
It is clear from our case series that the profound HL
experienced by these individuals can be correlated with
the massive loss of cochlear neurons in the presence of
preserved hair cells and other structures of the cochlear
duct. Although audiometric data are not available from
early childhood, all four individuals had enough hearing to
be able to develop language. Therefore, we infer that the
SNHL in MTS is likely to be the result of a postnatal,
progressive degeneration of cochlear neurons.
In addition to the severe loss of auditory and vestib-
ular ganglion cells, other histopathology abnormalities
were observed in some temporal bones such as chronic
otitis media (1 ear), partial atrophy of the organ of Corti (2
ears), and mild atrophy of the stria vascularis (1 ear).
Some of these changes were asymmetric, for example,
atrophy of the organ of Corti and strial loss between the
two ears of subject VI:24. The histopathologic changes in
any given temporal bone specimen represent the end re-
sult of insults accumulated over the lifespan of an indi-
vidual. These insults include, but are not restricted to, the
effects of genetic mutations, exposure to noise, potentially
ototoxic medications, trauma, infections, and systemic dis-
orders. It is difficult to ascertain the precise causes for
these other histopathologic abnormalities that were ob-
served in our cases.
The molecular basis for neural degeneration in MTS
is under investigation.
15,16
Neuronal cell loss has been
shown to occur within the optic nerve, retina, striate cor-
tex, basal ganglia, and dorsal roots of the spinal cord in
different individuals with MTS.
3
It has been shown that
expression of mitochondrial proteins is not uniform within
the central nervous system.
16
The DDP/TIMM8A protein
is prominently expressed in the soma and dendritic por-
tion of Purkinje cells within the brain. It has been shown
in mammals that the DDP/TIMM8A protein partners with
another TIMM protein (called TIMM13) to form a 70 kD
complex in the mitochondrial intermembrane space and
that this complex is part of a translocation apparatus for
the import and assembly of inner membrane proteins.
MTS is believed to result from defects in the assembly of
the DDP/TIMM8A-TIMM13 complex, leading to mitochon-
drial dysfunction in specific subsets of cells where this
protein is critical. Future work involving immunolocaliza-
tion of these proteins in various parts of the brain and ear,
as well as development of a suitable animal model, may
shed more light on the molecular pathogenesis of MTS.
The observed histopathologic changes in our tempo-
ral bones may be used to predict clinical features that may
alert a clinician to the occurrence of MTS in a child with
progressive SNHL. We would predict an audiometric find-
ing of loss of speech discrimination ability that is out of
proportion to the loss of pure-tone audiometric thresholds.
Although cochlear neuronal cells are critical for under-
standing speech, loss of up to 80% of cochlear neurons has
been shown to be consistent with normal pure-tone
thresholds, and losses of 90% create only moderate thresh-
old elevations.
7
One would also predict poor morphology of
auditory brainstem responses (ABRs) because ABRs are
critically dependent on a functioning cochlear nerve and
central auditory pathways. Otoacoustic emissions (OAEs)
would be preserved if the outer hair cells are intact, as was
clearly the case in two of our specimens. The presence of a
progressive SNHL in a male child with poor speech dis-
crimination scores, poor morphology of ABRs, intact
OAEs, and no other systemic abnormalities should prompt
a suspicion of MTS and appropriate genetic analysis.
There is a dearth of data in the literature concerning
the audiologic findings in MTS. Richter et al.
17
described
three children with X-linked agammaglobulinemia who
had large deletions within the Bruton tyrosine kinase
gene as well as a deletion of the whole TIMM8A gene.
These children suffered from progressive SNHL. Audio-
logic testing in two of these cases showed presence of
OAEs and absence of ABRs, which is consistent with what
one would predict from the otopathology observed in our
cases. On the other hand, Aguirre et al.
10
described two
brothers with SNHL and MTS, one of who had absent
ABRs and absent OAEs. One of the temporal bones in the
present study also showed loss of a large number of outer
hair cells, which could explain the absent OAEs. Addi-
tional well-documented audiologic and temporal bone his-
topathologic studies are necessary to define the complete
spectrum of abnormalities in MTS.
All five temporal bones examined showed a severe
loss of vestibular ganglion cells, consistent with a progres-
sive vestibular neuropathy caused by the MTS mutation.
Such degeneration probably evolved slowly over time,
which may allow for central compensation and may ex-
plain the absence of significant vestibular complaints in
the medical histories of our subjects. However, it is likely
that the vestibular degeneration resulted in bilateral pe-
ripheral vestibular hypofunction, and it probably contrib-
uted to the imbalance and ataxia experienced by these
patients later in life.
Our histopathologic findings also have implications
for management of HL in MTS. The severity of auditory
neuropathy in our cases suggests that amplification may
provide limited benefit. It is more difficult to speculate
whether cochlear implantation may be beneficial. Al-
though it is traditionally assumed that implant perfor-
mance is related to the number of surviving cochlear neu-
ronal cells, temporal bone histopathologic studies have
failed to show a positive correlation between implant per-
formance and numbers of cochlear neuronal cells.
18,19
It is
possible that implantation early in life while stimulable
auditory nerve fibers are still available may be of benefit
in children with MTS. Indeed, cochlear implantation has
been successful in other cases of auditory neuropathy.
20–22
Another potential avenue for future rehabilitation and
treatment is regeneration of cochlear neurons and of the
auditory nerve using therapies based on stem cells. The
histopathologic finding that the organ of Corti and other
end-organ structures of the cochlear duct are generally
intact makes this a particularly attractive avenue for fu-
ture research. Discovery of molecular targets within mi-
Laryngoscope 117: July 2007 Bahmad et al.: Otopathology in Mohr-Tranebjærg Syndrome
1207
tochondrial cochlear neuronal cells may also provide the
basis for future novel therapeutic interventions.
SUMMARY AND CONCLUSIONS
We described the otopathology in four individuals
affected with the Mohr-Tranebjærg syndrome (MTS), an
X-linked, recessive, syndromic, sensorineural HL caused
by a mutation in the DDP/TIMM8A gene. The otopathol-
ogy was strikingly similar in that all temporal bones ex-
amined showed near-total loss of cochlear neuronal cells
and severe loss of vestibular neurons. We infer that the
HL in MTS is likely to be the result of a postnatal and
progressive degeneration of cochlear neurons and that
MTS constitutes a true auditory neuropathy. Our findings
have implications for clinical diagnosis of patients with
MTS and management of the HL.
Acknowledgments
The authors thank Mr. Axel Eliasen and Mr. Lak-
shmi Mittal for support of our work.
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