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Achondroplasia: Morphological change of the skull base
Poster No.:
C-1164
Congress:
ECR 2015
Type:
Educational Exhibit
Authors:
Y. Nakai, H. Yokota, K. Takezawa, H. Nakajima, K. Kosaka, K.
Yamada; Kyoto/JP
Keywords:
Ear / Nose / Throat, Bones, CT, Education, Dysplasias
DOI:
10.1594/ecr2015/C-1164
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Learning objectives
To learn process of how the skull base generates and to know detailed and substantial
morphologic changes on the skull base that is occurred in achondroplasia with
embryology
Background
Achondroplasia is the most common skeletal dysplasia. It is caused by FGFR3 gene
and MAPK signaling changes. Hypoplasia of the skull base can cause neurological
complications in achondroplasia. Previous studies have shown that the small foramen
magnum is implicated in sudden death and temporal bone rotation is partially related to
hearing loss. Although there have been many papers studying specific locations, merely
few reviews of imaging findings have been reported so far. Here, therefore, we make the
comprehensive review of morphological changes on the skull base by achondroplasia,
including embryology.
Findings and procedure details
1. Anatomy and development of the skull
Terminology used to describe the embryology of the skull base is somewhat complicated,
and may need some explanation, There are three different categories of classifications;
1) locations of the skull, 2) type of ossification and 3) mesenchymal origin. One has to
be aware that each term used to describe the same location does not necessarily match
within the above mentioned three different categories.
- We would like to first mention about the anatomical locations of the skull bones. The
skull can be divided into the neurocranium and viscerocranium. The former covers and
protects the brain and the latter compose the facial bones.
- The second category is about the type of ossification. Most parts of the cranium
are made by membranous ossification. On membranous ossification, immature
mesenchymal cells evolve into osteoblasts that create bone. On the other hand, the
skull base is made by endochondral ossification. On endochondral ossification, immature
mesenchymal cells evolve into chondroblasts and then chondrocytes that create cartilage
template that turns into bone through the complex steps.
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Fig. 1: Lateral and basal views of the skull: The skull parts are color coded based on
the nomenclature combining the first with the second issues described above. Orange,
cartilaginous neurocranium; green, membranous neurocranium; gray, membranous
viscerocranium.
References: - Kyoto/JP
- The third category is about the mesenchymal origin, the skeletal structures of the head
and face are derived from neural crest, lateral plate mesoderm and paraxial mesoderm.
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Fig. 2: Lateral view and base of the skull: Blue, neural crest origin; red, paraxial
mesoderm origin.
References: - Kyoto/JP
To understand the morphologic change on the skull base in ACH, the second category
is especially important. Below, we will summarize the clinical significance of these three
classifications.
A. Neurocranium
i. Cartilaginous neurocranium
This term indicates part of the neurocranium made by endochondral ossification.
Cartilaginous neurocranium includes most parts of the skull base and the occipital bone. It
is derived from neural crest and paraxial mesoderm, whose borderline is the sella turcica.
The skull base is formed mainly from the fusion of hypophyseal plate and parachordal
plate. The hypophyseal plate is derived from neural crest and the parachordal plate is
derived from paraxial mesoderm. Ossification of the cartilaginous plate proceeds in order
of the occipital, sphenoid and ethmoid bones.
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ii. Membranous neurocranium
The roof and most parts of the sides of the skull; the calvaria are derived from neural
crest and paraxial mesoderm. The borderline is the coronal and squamosal sutures.
Membranous neurocranium undergoes membranous ossification. Bone spicules are
formed from ossification centers and will finally form flat bones.
B. Membranous viscerocranium
The squamous temporal bone, maxilla and mandibule undergo membranous ossification.
One has to be aware of the fact that the petrous part of the temporal bone and auditory
ossicles are composed by endochondral ossification.
2. Why FGFR3 gene mutation causes morphologic change on the skull base?
ACH is known to occur from FGFR3 gene mutation, which effects FGFR3 signalling in
chondrocytes. The mutation leads to limited proliferation of chondrocyte and accelerated
bone formation. The development of the skull base occurs mainly at the synchondroses,
including intersphenoid, sphno-occipital and intraoccipital synchondroses. FGFR3
mutation accelerates ossification of cartilages in these synchondroses and causes early
closure. This early closure can be the main reason of hypoplasia of the skull base in ACH.
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Fig. 3: The anatomy of the skull base. There are some synchondroses of the intra- or
inter-bones of the skull base.
References: - Kyoto/JP
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Fig. 4: FGFR3 gene mutation increases FGFR3 signalling. It causes early
closure of synchondroses via the two pathways. The target of FGFR3 signalling
stimulation is chondrocytes. FGFR3 signalling suppresses their proliferation and
leads to accelerated hypertrophic differentiation. In addition, it induces secretion
of Bmp from chondrocytes. Bmp secretion results in accelerated bone formation
vis osteoblasts and osteoprogenitor cells. This pathway is partially mediated by
MAPK.
References: - Kyoto/JP
3. Imaging findings of the skull base on achondroplasia
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Fig. 5: Summary of imaging findings on ACH.
References: - Kyoto/JP
I. Early closure of synchondroses
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Fig. 6: Left column, case with ACH; right column, normal control of the same age. The
spheno-occipital (orange) and intraoccipital synchondroses (blue) are already fused.
References: - Kyoto/JP
II. Small posterior cranial fossa
Small posterior cranial fossa can be the cause of hydrocephalus and sometimes sudden
death.
a. Small foramen magnum having a tail and short clivus
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Fig. 7: The foramen magnum is narrowed, causing compression on the cervical cord
(orange arrows). This can lead to sudden death. Note that the clivus is very short,
while the supraoccipit (yellow cf. Fig. 3) is not relatively spared, because posterior and
lateral margins of the supraoccipit grows by membranous ossification. Tail-like notch is
often demonstrated at posterior margin of foramen magnum (blue), which implies early
fusion of intraoccipital synchondroses.
References: - Kyoto/JP
b. Narrowing of the jugular foramen
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Fig. 8: The jugular foramen is located between the temporal and occipital bones.
Failure of endochondral ossification affects both the bones and causes narrowing of
the jugular foramen.
References: - Kyoto/JP
c. Enlargement of collateral veins
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Fig. 9: The mastoid emissary vein is prominent. In addition, leptomeningeal veins are
enlarged in the convex. They have a role as collateral veins.
References: - Kyoto/JP
d. Hydrocephalus
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Fig. 10: Elevated venous pressure may interrupt absorption of cerebrospinal fluid
(CSF) and cause hydrocephalus. Narrowing of the foramen magnum also interferes
with CSF flow and may be another cause of hydrocephalus.
References: - Kyoto/JP
e. Foreshortening of the carotid canals
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Fig. 11: The carotid canal is shortened while the diameter is preserved.
References: - Kyoto/JP
III. Distortion of the skull base
The skull base is distorted due to imbalance between cartilaginous and membranous
neurocraniums. The distortion of the temporal bone can cause hearing loss.
a. Towering petrous ridge Normal
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Fig. 12: The medial part of the bilateral petrous bones are elevated (arrows). The
medial part of the petrous bone is strongly influenced by endochondral ossification.
On the other hand, the influence for the lateral part is milder than the medial. The
imbalance can cause towering petrous ridge.
References: - Kyoto/JP
b. Rotation of the temporal bone structures
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Fig. 13: Towering petrous ridge can be accompanied by rotation of the structures in
the temporal bone, including the auditory ossicles. The rotation can cause conductive
hearing loss. Note however, that sensorineural or mixed hearing loss is often observed
in ACH. Microscopic inner ear abnormalities may be associated with the sensorineural
hearing loss.
References: - Kyoto/JP
c. Poor development of the mastoid air cell
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Fig. 14: Patients with ACH often have otitis media and mastoiditis (arrows) due to
eustachian tube dysfunction. This can be another cause of hearing loss.
References: - Kyoto/JP
Conclusion
Understanding vital morphologic changes on the skull base with embryology helps you
to know various neurological complications in achondroplasia.
Personal information
References
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