eEdE#: eEdE-134
Morphological Change
on Skull Base
by Achondroplasia
Yoshitomo Nakai, Hajime Yokota,
Kayu Takezawa, Hisakazu Nakajima,
Kitaro Kosaka, Kei Yamada
Department of Radilogy,
Kyoto Prefectural University of Medicine
Background
Achondroplasia(ACH) is a typical disease of
dwarfism. FGFR3 gene mutation causes
failure of endochondral ossification in ACH.
The skull base development is interfered by
the mutation, while the cranium is spared
because it is composed with membranous
ossification. Here, we show the morphologic
changes on ACH associated with
embryology of the skull.
Findings and procedure details
Anatomy and development of the skull
Terminology is complicated in embryology of the
skull. Locations of the skull, type of ossification
and mesenchymal origin are included in the terms
to explain developmental course of the skull base.
Be careful that each term doesn’t match to the
other ones.
The first, on locations of the skull, the skull can be
divided to the neurocranium and viscerocranium. The
former covers and protects the brain and the latter
composed the face.
The second, on type of ossification, the 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.
The third, on mesenchymal origin, the skeletal
structures of the head and face are derived from neural
crest, lateral plate mesoderm and paraxial mesoderm.
Squamous part
of
Temporal bone
Frontal
bone
Parietal
bone
Nasal bone
Occipital bone
Fossa hypophysialis
Maxilla
Zygomatic bone
Maxilla
Petrous part
of
temporal bone
Foramen
magnum
Lateral view and base of the skull:
Blue, neural crest origin Yellow, paraxial mesoderm origin.
Purpose
To understand morphologic change on the skull
base by ACH, the second is especially important.
Here, we summarize these three classifications.
A. Neurocranium
i. Cartilaginous neurocranium
This name means a part of neurocranium made by endochondral ossification.
Cartilaginous neurocranium including most of the skull base and the occipital bone.
Occipital bone
Ethmoid
bone
Sphenoid
bone
Petrous
Petrous part
of
Occipital
temporal bone bone
part
of
temporal
bone
Skull base and occipital bone are derived from neural crest and paraxial mesoderm,
whose borderline is the sella turcica. The skull base is formed mainly from fusion of the
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.
A. Neurocranium
ii. Membranous neurocranium
•
The roof and most of 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
center and finally flat bones develop.
Frontal bone
Frontal bone
Parietal
bone
Parietal
bone
B. Membranous viscerocranium
The squamous temporal bone, maxilla and mandibule
undergo membranous ossification. Be careful that the
petrous part of the temporal bone and auditory ossicles are
composed by endochondral ossification.
Squamous part
of
Temporal bone
Squamous part
of
Temporal bone
Nasal
bone
Maxilla
Zygomatic
bone
Maxilla
Why FGFR3 gene mutation causes
morphologic change on the skull
base?
ACH is due to FGFR3 gene mutation, which effects FGFR3 signalling in
chondrocytes. The mutation brings limiting proliferation of chondrocyte
and accelerating bone formation. The development of the skull base
occurs mainly at the synchondroses, including intersphenoid, sphnooccipital and intraoccipital synchondroses. FGFR3 mutation accelerates
ossification of cartilages in these synchondroses and causes early closure.
Early closure can be the main reason to hypoplasia of the skull base on
ACH.
Sphenoid bone
Speno-occipatal
synchondrosis
Basioccipital
Anteriorintraoccipital
Exoccipital
The anatomy of the skull base. There are some
synchondroses of the intra- or inter-bones of the skull
base.
syncondrosis
Occipital bone
Posteriorintraoccipital
syncondrosis
Proliferation
FGFR3
Accelerated
hypertrophic
differentation
Bmp-2,7
MAPK
Vegf
Vascular
invasion
Vascular
cells
Bone
formation
Osteoblasts
Osteoprogenitor
cells
FGFR3 gene mutation increases FGFR3 signalling. It cause early closure of synchondroses and
unification of ossification. The target of FGFR3 signalling stimulation is chondrocytes. FGFR3
signalling suppresses their proliferation and accelerated hypertrophic differentiation. In addition, it
induces secretion of Bmp from chondrocytes. Bmp secretion results in bone accelerated bone
formation vis osteoblasts and osteoprogenitor cells. This pathway is partially mediated by MAPK.
Increased Fgfr3 signaling also causes upregulation of Vegf in chondrocytes, promoting vascular
invasion. It would accelerate synchondrosis clousere while increased bone formation would
accelerate the fusion of ossification centers.
FGFR3
mutations
Summary of imaging findings on ACH
Early closure of spheno-occipital
and occipital bone synchondroses.
Narrowing of the jugular foramen
Distortion of the skull base
Stenosis of foramen magnum
Dysplasia of temporal bone
Sudden death
・Poor development of the mastoid air cells
・poor eustachian tube function
Hearing loss
otitis media
・Hydrocephalus
・Emissary foramina enlargement
・Towering petrous ridges.
・Rotation of the temporal bone structures
I. Early closure of synchondroses
FGFR3 mutation accelerates ossification of the synchondroses.
Left column, case with ACH; right column, normal control of the same age.
The spheno-occipital (orange) and intraoccipital synchondroses (blue) are
already fused.
II. Small posterior cranial fossa
Small posterior cranial fossa can cause sudden death and hydrocephalus.
a. Small foramen magnum having a tail and short clivus
Clivus
Tail
The foramen magnum is small, causing compression to the medullocervical
junction(orange). It is related to sudden death.
Tail-like notch is often demonstrated at posterior margin (blue). It implies early fusion of
intraoccipital synchondroses and influence by membranous ossification of the
supraoccipit. Note clivus is very short, while the supraoccipit is not relatively affected,
because posterior and lateral margins of the supraoccipit are influenced by membranous
ossification. The tail may be formed by imbalance of elongation of the bones.
b. Narrowing of the jugular foramen
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.
c. Enlargement of collateral veins
The mastoid emissary vein is prominent.
In addition, leptomeningeal veins are
enlarged in the convex. They have a role of
collateral veins.
Petrous part
of
temporal bone
Jugular foramen
Sigmoid sinus
Occipital bone
Emissary vein
d. Hydrocephalus
e. Foreshortening of the carotid canals
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.
The carotid canal is shortened though
the diameter is preserved. Note the
carotid canal is involved in the
sphenoid bone
Carotid
canal
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
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.
b. Rotation of the temporal bone structures
Towering petrous ridge
accompany rotation of the
structures in the temporal
bone, including the
auditory ossicles. The
rotation can cause
conductive hearing loss.
However, note that
sensorineural or mixed
hearing loss is often
observed on ACH.
Microscopic inner ear
abnormalities may be
associated with
sensorineural hearing loss.
The mechanism of distortion
Petrous part of
the temporal bone
Schema of the skull base
Green, endochondral ossification; Red, membranous ossification
Note imbalance between the central part composed by endochondral
ossification and the peripheral part composed by membranous ossification.
The imbalance causes bending and distortion of the petrous part of the
temporal bone．
c. Poor development of the mastoid air cell
Patients with ACH often have otitis
media and mastoiditis (arrows) due
to eustachian tube dysfunction.
They can also cause hearing loss.
The eustachian tube is involved in
the temporal bone
Conclusion
Understanding vital morphologic
changes on the skull base with
embryology helps you to know
various neurological complications
in ACH.
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