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CHAPTER
32
Hearing Lo
ss in Osteogenesis
Imperfecta
Joseph P. Pillion
1
, Felipe Santos
2
, David M. Vernick
2
and Jay
Shapiro
1
1
Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, USA,
2
Harvard Medical School, Boston, MA, USA
INTRODUCTION
can be seen in the malleus, incus and stapes crura.
Microfractures can also be seen in the otic capsule.
10
The
crura of the stapes can be thin and deformed. The foot-
plate of the stapes can be fixed in the oval window with
bony changes that range from calcification of the annular
ligament to thick fibrocartilage replacement of the foot-
plate. These histologic changes suggest quantitative and
qualitative defects in type 1 collagen and may induce or
increase the susceptibility to abnormal remodeling in the
temporal bone. The observed otosclerotic lesions can be
Osteogenesis imperfecta (OI) affects type 1 collagen -
the most abundant protein in the body. Ninety-five per-
cent of all OI cases involve a dominantly transmitted
mutation of COL1A1 or COL1A2 genes. These genes are
responsible for the synthesis of the pro-alpha-1 and pro-
alpha-2 polypeptide chains that form the type 1 collagen
triple helix.
1
The remaining 5% of OI cases involve reces-
sive mutations associated with severe or lethal OI. These
genes modify the intracellular processing of type 1 col-
lagen: CRTAP (collagen-related protein), P3H1/LEPRE1
(prolyl 3-hydroxylase 1) and PPIB (Cytophyllin B pro-
tein), and several chaperone proteins such as HSP-47 in
the endoplasmic reticulum.
2-4
CRTAP and P3H1 form a
complex with cyclophilin B (CyPB)d in the endoplasmic
reticulum which 3-hydroxylates the Pro986 residue of
collagen pro-alpha 1 and pro-alpha 2 chains.
5
Mutations
of these genes lead to severe or fatal skeletal disease (OI
types VII and VIII).
6
No correlation has been established
to date between any of these mutations though and the
degree of hearing loss in OI.
7-9
T
EMPORAL BONE FINDING
S
Histopathologic examination of the temporal bones
in OI shows some distinct bony changes.
10
There is evi-
dence of deficient and abnormal ossification of the otic
capsule bone. Delayed patterns of ossification in type II
OI and otosclerotic lesions in non-type II OI are char-
acteristic features of the histopathology (
Figures 32.1
and 32.2
). The ossicles and middle ear may show signs
of abnormal and deficient ossification. Microfractures
FIGURE 32.1
A hematoxylin and eosin-stained cross-section of
a temporal bone in a patient with type I OI. This patient had a con-
ductive hearing loss that progressed to a mixed hearing loss during
late adulthood. The cochlea is surrounded by a darker blue stain cor-
responding to the otosclerotic lesion. Beneath the cochlea there is an
area of cavitation. The asterix indicates the silhouette of a surgically
placed stapes prosthesis to correct the conductive hearing loss.
