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- Abnormalities of bone and/or cartilage growth
- Because of abnormal gene expression,
phenotypes continue to evolve throughout
- Altered blastogenesis in first 6 weeks of IU life
- Phenotype fixed
•Skeletal dysplasias are a heterogeneous group of
conditions associated with various abnormalities
of the skeleton.
•These conditions are caused by widespread
disturbance of bone growth, beginning during the
early stages of fetal development and evolving
•Despite recent advances in imaging, fetal
skeletal dysplasias are difficult to diagnose in
utero due to a number of factors, including
the large number of skeletal dysplasias and
their phenotypic variability with
lack of precise molecular diagnosis for
Lack of a systematic approach
the inability of ultrasonography (US) to provide
an integrated view,
variability in the time at which findings
in some skeletal dysplasias.
•US of suspected skeletal dysplasia involves
systematic imaging of the long bones, thorax,
hands and feet, skull, spine, and pelvis.
•Assessment of the fetus with three-dimensional
US has been shown to improve diagnostic
accuracy, since additional phenotypic features not
•The radiologist plays a major role in making an
accurate diagnosis; however, representatives of other
disciplines, including clinicians, molecular biologists,
•Skeletal dysplasias are a heterogeneous group of
conditions associated with abnormalities of the
skeleton, including abnormalities of bone shape, size,
and density, that manifest as abnormalities of the
limbs, chest, or skull.
• Over the past 30 years, the classification of
skeletal dysplasia has evolved from one based on
clinical-radiologic-pathologic features to one that
includes the underlying molecular abnormality for
conditions in which the genetic defect is known.
• In 1977, the European Society of Pediatric
Radiology adopted the international nomenclature
of constitutional-intrinsic bone disease.
•This nomenclature was modified in 1983, 1997, and
2001. The major change in 2001 was the addition of
• Dysostoses occur singly or in combination.
disturbance of bone growth, beginning during the
early stages of fetal development and evolving
throughout life due to active gene involvement. The
five original categories have been expanded to 32
International Classification of
Osteochondrodysplasias, published in 2002
Classified1. Osteochondrodysplasias - 33 groups (Groups
2. Dysostoses – 3 (Groups A–C)
- A - predominantly craniofacial involvement
- B - predominant axial involvement
- C - predominant involvement of hands & feet
•on the classification of constitutional disorders
of bone, of which approximately 50 are apparent
and identifiable at birth.
• Because they may be detected before birth,
these conditions are of particular importance to
• The prevalence of skeletal dysplasias (excluding
limb amputations) is estimated at 2.4 per 10,000
• The overall prevalence of skeletal dysplasias among
perinatal deaths was 9.1 per 1000 cases.
• Despite recent advances in imaging, fetal skeletal
dysplasias are difficult to diagnose in utero.
• Some of the factors that lead to difficulty in
diagnosis are the large number of skeletal
dysplasias and their phenotypic variability with
overlapping features, lack of precise molecular
diagnosis for many disorders, lack of a systematic
approach, the inability of ultrasonography (US) to
provide an integrated view such as an overt
clinical inspection can offer, and variability in the
time at which findings manifest in some skeletal
•Prenatal diagnosis is easier in the presence of a
positive family history and a precise description of the
phenotype, since many disorders are inherited as
autosomal dominant or recessive disorders.
•It is also not unusual for skeletal dysplasia to first be
suspected during routine US examination after a
shortened long bone or abnormal skeletal finding has
•In addition to delineating the differential diagnosis,
it is important to recognize possible lethality on the
basis of US findings, including chest circumference,
femur length-abdominal circumference ratio, the
presence of “cloverleaf skull,” and so on.
•US is the primary method for imaging a fetus.
•US technique for assessing fetal skeletal dysplasia;
•discuss and illustrate the US diagnosis of skeletal
dysplasias such as
chondrodysplasia punctata, and
diastrophic dysplasia; and
•briefly review postnatal evaluation in affected
Imaging Approach : Antenatal US
- Long bones lengths
- Absence and malformation
- Hypoplasia : Rhizomelia, Mesomelia, Rhizo-
- Curvature, degree of mineralization, and fractures
- The femur length–abdominal circumference ratio
(<0.16 - lethal outcome)
- Femur length–foot length ratio (normal = 1, <1
suggests skeletal dysplasia/Trisomy 21)
•The long bones in all of the extremities should be
•If limb shortening is present, the segments involved
should be defined.
•A detailed examination of the involved bones is
necessary to exclude absence, hypoplasia, and
malformation of the bones.
•The bones should be assessed for presence,
curvature, degree of mineralization, and fractures.
• The femur length-abdominal circumference ratio
(<0.16 suggests lung hypoplasia) and femur
length-foot length ratio (normal = 1, <1 suggests
skeletal dysplasia) should be calculated.
•The chest circumference and cardiothoracic ratio
should be measured at the level of the four-chamber
view of the heart.
• ~ 11 weeks : 0.38
• ~ 17 - 20 weeks : 0.45
term : 0.5
• A chest circumference less than the 5th percentile for
gestational age has been proposed as an indicator of
•Other parameters used are a chest
ratio less than the 5th percentile , chest
area, a heart area-chest area ratio less
than the 5th percentile, a chest-trunk
length ratio less than 0.32 , and a femur
length-abdominal circumference ratio less
than 0.16 .
•Hypoplastic thorax occurs in many skeletal dysplasias
such as thanatophoric dysplasia, achondrogenesis,
hypophosphotasia, camptomelic dysplasia,
chondroectodermal dysplasia, osteogenesis
imperfecta, and short-rib polydactyly and may lead to
pulmonary hypoplasia, which is the main cause of
neonatal death in many lethal skeletal dysplasias .
•The shape and integrity of the thorax should be
noted. Abnormal rib size and configuration are
also seen in patients with lethal skeletal
•The clavicles should be measured, since
absence or hypoplasia of the clavicles is seen
in cleidocranial dysplasia. The presence of the
scapula should also be noted, since its absence
is a useful defining feature of camptomelic
Chest–trunk length ratio less than 0.32
Femur length–abdominal circumference ratio less
Hypoplastic thorax occurs in – lethal dysplasia, e.g.
thanatophoric dysplasia, achondrogenesis,
Hands and Feet
• The hands and feet should be evaluated to exclude the
presence of (a) pre- or postaxial polydactyly (the
presence of more than five digits; preaxial if the extra
digits are located on the radial or tibial side and postaxial
if they are located on the ulnar or fibular side); (b)
syndactyly (soft-tissue or bone fusion of adjacent digits);
(c) clinodactyly (deviation of a finger); and (d) other
Ultrasound Clinodactyly, right hand Hypoplastic middle
phalanx in the right 5th finger indicated by the arrow.
• Foot length should be measured and any missing
bones evaluated. Any postural deformities such as
“hitchhiker‟s thumb,” “rocker-bottom” feet, and
clubbed feet or hands should also be evaluated.
• Clubbing of the hand is suggestive of the
spectrum of “radial ray” anomalies, which include
an abnormal thumb (Holt-Oram syndrome),
hypoplasia and absence of the thumb, and
sometimes, absence of the radius or of both the
radius and the hand.
Second-Trimester Sonographic Diagnosis of
Hands and Feet
Pre- or postaxial polydactyly
The Hitchhiker's Thumb consists of :
•Oval and hypoplastic first metacarpal.
•Abducted proximally positioned thumb.
•Low set first digit.
1.Skeletal dysplasia • Diastrophic dysplasia.
2.Isolated and familial (15%).
3.Trisomy 18 (30%) and trisomy 13.
4.Fetal akinesia and arthrogryposis.
6.Limb-body wall complex (32%).
It is characterized by a prominent calcaneus (heel) and a
convex rounded sole. The presence of a rocker bottom foot in
an antenatal ultrasound scan is sometimes classified as a soft
sign for aneuploidic anomalies 3
•Head circumference and biparietal diameter should be
measured to exclude macrocephaly.
•The shape, mineralization, and degree of ossification of
the skull should be evaluated. Interorbital distance
should be measured by using the binocular diameter
and interocular diameter to exclude hyper- or
•Other features such as micrognathia, short upper lip,
abnormally shaped ears, frontal bossing, and
cloverleaf skull should be assessed.
•Deviations from the normal shape of the head,
including brachycephaly (anteroposterior shortening
of the head), scapocephaly (lateral flattening of the
head), and craniosynostoses (premature fusion of the
sutures), should be noted.
The inter-ocular distance (IOD) is a measurement between
the two medial canthi of each eye
•The spine should be carefully imaged to assess the
relative total length and the presence of curvature to
•Mineralization of vertebral bodies and neural arches
should be evaluated. Vertebral height should be
subjectively evaluated for platyspondyly (flattened
vertebral body shape with reduced distance between
the endplates), which is typically seen in
thanatophoric dysplasia, However, platyspondyly
may be difficult to identify even for the experienced
•The shape of the pelvis can be important in certain
dysplasias and dysostoses, such as limb-pelvic
hypoplasia; femoral hypoplasia-unusual face syndrome
(hypoplastic acetabulae, constricted iliac base with
vertical ischial axis, and large obturator foramina);
achondroplasia (flat, rounded iliac bones with lack of
iliac flaring; broad, horizontal superior acetabular
margins; and small sacrosciatic notches); and so on.
•Pelvic shape may be difficult to evaluate at
routine US, and three dimensional (3D) US may
• Assessment of the fetus with 3D US has been
shown to improve diagnostic accuracy, since
additional phenotypic features not detectable at
two-dimensional US may be identified .
RG ■ Volume 28 • Number 4
Long bones -
Dighe et al 1063
All long bones to be measured
Standard measurement for wks
Chest circumference to be obtained Measurement of the four chamber view of the heart
at the level
Normal measurement for wks
Any bones missing?
Feet - Yes / No Hands -Yes
/ No Polydactyly
Chest Cir/ Abdominal Cir
measurement of clavicles at wks
Hands and feet Foot
Shape of thorax Bell Shaped - Yes / No
Syndactyly Yes /No Postural
Clubfeet Yes / No Clubhand
Yes / / No
Micrognathia: YesNo Short upper lips: Yes /
measurement of foot at wks
No Abnormally shaped ears: Yes / No
Normal = 1
Fetal Motion - Normal / Decreased AFI - Normal /
Decreased / Increased
Skull and Face:
Macrocrania: Yes / No
Mineralization of skull bones: Normal / Decreased
Relative length - Normal / Decreased
Mineralization of vertebral bodies - Normal /
Frontal bossing: Yes / No
Vertebral Height - Normal / Decreased
Biorbital diameter - Distance between the inner margins of the orbits
Normal measurement of biorbital diameter at_ wks
Any other organ abnormality:
3D dataset of the following to be acquired:
1. Face (profile view to look at the facial features)
2. Chest (transverse and sagittal 3D dataset from anterior aspect preferably to calculate lung volumes for pulmonary hypoplasia)
3. Hand (one only)
4. Foot (one only)
5. Pelvis (transverse 3D dataset from anterior aspect for iliac flaring)
6. Spine (sagittal 3D dataset to look at the vertebral height)
Figure 1. Worksheet used in the Department of Radiology and Obstetrics at the
University of Washington Medical Center while imaging a fetus with suspected skeletal
Diagnosis with US
If the limbs are disproportional (Figs 2-5), the
following questions should be addressed:
1. Does the abnormality affect the proximal
middle (mesomelic), or distal
2. Is polydactyly, ectrodactyly, clinodactyly, or
3. Are there any fractures, curved bones, or joint
deformities, or clubbing of the foot or hand?
4. Are metaphyseal changes present?
5. Is there a premature appearance of ossification
6. Are there any hypoplastic or absent bones?
Figure 3. Diagram illustrates a diagnostic algorithm for
use in fetuses with moderate limb shortening and
normal mineralization. OI = osteogenesis imperfecta.
Figure 4. Diagram illustrates a diagnostic algorithm for use in fetuses
with mild limb shortening and normal mineralization and in fetuses with
partial or complete limb agenesis. OI = osteogenesis imperfecta.
algorithm for use in fetuses with normal or
shortened limbs and decreased mineralization. OI
= osteogenesis imperfecta.
If the spine is mainly affected, one should ask the
1.Is the spine short because of missing parts (eg,
2. Is there abnormal curvature?
3. Is there shortening of vertebral bodies?
4. Are all parts of the spine equally affected
5. Is platyspondyly present (thanatophoric
6. Is the spinal canal of normal width?
7. Are any meningomyeloceles present?
If the thorax is mainly affected (Fig 6), the following
questions should be addressed:
1. Is the thorax extremely small (thanatophoric
2. Is the thorax long and narrow (Jeune syndrome)?
3. Are the ribs extremely short (short-rib polydactyly)?
4. Are fractures present (osteogenesis imperfecta type
5. Is there clavicular aplasia, hypoplasia, or
6. Is the scapula normal or abnormal (camp-tomelic
7. Are there any gaps between ribs (Jarcho-Levine
Figure 6. Diagram illustrates a diagnostic algorithm for use in
abnormalities. OI = osteogenesis imperfecta.
Figure 7. Diagram illustrates a diagnostic algorithm for use in
abnormalities. OI = osteogenesis imperfecta.
Figure 8. Diagram illustrates a diagnostic algorithm for
use in fetuses with suspected skeletal dysplasia and
skull abnormalities. OI = osteogenesis imperfecta.
Examples of Fetal Skeletal Dysplasia
The overall prevalence of limb deficiency (Fig 9) is
approximately 0.49 per 10,000 births. Most are simple
transverse reduction deficiencies of one forearm or
hand without associated anomalies. The remainder
consist of multiple reduction deficiencies, with
additional anomalies of internal organs or
•Isolated extremity amputation can be due to amniotic
band syndrome, exposure to a teratogen, or vascular
•In most cases, the anomaly is sporadic, and risk of
recurrence is negligible.
Figure 9. Isolated limb deficiency. (b) US images show a shortened
forearm with an abnormal hand (arrow) (note the lack of a normal
hand and the abnormal soft tissue at the distal end of the forearm),
normal limb bone echogenicity, and otherwise normal anatomy.. (c)
Radiograph shows abnormal bone tissue (arrow) at the end of the
normally formed and mineralized forearm bone.
•all limb deficiencies occur in patterns and can
be grouped and classified according to the
system of Swinyard and Marquardt, which is a
modification of the classification system of
Frantz and O‟Rahilly.
• In this system, only two basic terms are used:
amelia, indicating complete absence of a limb;
and meromelia, indicating partial absence of a
•All deficiencies are classified as either terminal
(absence of all skeletal elements along a
longitudinal ray beyond a given point) or intercalary
(absence of the proximal or middle segment of a
limb with all or part of the distal segment present).
•Further sub grouping is based on the axis of
deficiency (transverse or longitudinal) and the
individual bones involved.
•The term “thanatophoric dysplasia” is derived from
the Greek word thanatophoros, which means “bearing
•Thanatophoric dysplasia is themost common lethal
skeletal dysplasia. Langer et al separated this
condition into two types: type 1 (Fig 10) and type 2
•Both types are caused by mutations of the geneencoding fibroblast growth factor receptor 3
• Inheritance is generally autosomal dominant .
•Thanatophoric dysplasia is characterized by
disproportionate dwarfism with very short
extremities, which are bowed in type 1 and may be
•The trunk length is normal, but the thorax is narrow.
•There is distinct flattening of vertebral ossification
centers (platyspondyly) (less severe in type 2 than in
type 1), as well as a disproportionately large head,
depressed nasal bridge, prominent forehead, and
protruding eyes .
•Secondary skull deformity is often present due to
the premature closure of cranial sutures.
•Cloverleaf skull deformity is generally seen in
type 2 .
• Polyhydramnios is present in almost 50% of
•Death occurs in early infancy in the majority of
cases due to respiratory insufficiency from
Figure 10. Thanatophoric dysplasia type 1. (a) Transverse US image shows a normal-shaped but
enlarged head. (b) Sagittal US image shows a depressed nasal bridge (arrowhead), a prominent
forehead (double arrows), and an undersized thorax (single arrow) compared with the abdomen.
(c) US image shows a telephone receiver-shaped femur (arrows). Normal limb echogenicity with
severe shortening and bowing of the limbs, a narrow chest, and macrocephaly suggest
thanatophoric dysplasia type 1 according to the diagrams in Figures 2, 6, and 8,
respectively. (d) Postmortem radiograph shows bowed long bones (white arrows), a narrow
chest, and platyspondyly (black arrow). (e, f) Autopsy photographs show shortened limbs, the
depressed nasal bridge (arrowhead in f), a short trunk, an enlarged abdomen, and the
prominent forehead (arrows in f).
Figure 11. Thanatophoric dysplasia type 2. (a) Axial US image shows an
oversized head with a cloverleaf shape (arrows). (b) Sagittal US image
shows a temporal bulge (arrow). (c) US image shows a “trident” hand.
Normal limb echogenicity with severe shortening, a narrow chest, and an
irregular shape of the head suggest thanatophoric dysplasia type 2
according to the diagrams in Figures 2, 6, and 8, respectively. (d) US
image shows a short but relatively straight long bone. (e) Coronal US
image through the abdomen-chest shows a hypoplastic thorax (arrow). (f)
Radiograph shows the cloverleaf skull shape created by the temporal bulge
in the skull (arrow). (g, h) Postmortem photographs show the prominent
forehead; the typical temporal bulge, resulting in the cloverleaf skull
shape (double arrows); and the trident hand (single arrow in h). Note the
bulge in the occipital region, a finding that represents an occipital
encephalocele (an unusual finding in thanatophoric dysplasia).
•The term “osteogenesis imperfecta” (Fig 12) refers to
a clinically, radiologically, and genetically
heterogeneous group of disorders caused by
mutations in genes that encode type I collagen,
leading to increased bone fragility
•The overall prevalence of osteogenesis imperfecta is
•The classification of osteogenesis imperfecta was
first proposed by Sillence, whose system was
subsequently modified by Byers et al .
•The mutations that cause osteogenesis
imperfecta are generally new mutations and are
inherited in an autosomal dominant pattern, except
for rare instances of type III disease that are
inherited in an autosomal recessive pattern .
•The fetal movements may be reduced .
•The skull may be thinner than usual, and the
weight of the US probe may deform the head
quite easily. In severe cases, the cranial vault has
a wavy outline and is easily compressed.
• Variations in the number of fractures, time of
presentation of patients with fractures (prenatal or
postnatal), secondary deformities, and soft-tissue
changes result in a wide variety of clinical and
radiologic phenotypes, which are presently grouped
according to the Sillence classification system.
•The major radiologic features of osteogenesis
imperfecta are generalized osteoporosis, retarded
calvarial bone formation, wormian bones, collapsed
vertebral bodies, rib fractures, thin cortex in tubular
bones, and, in more severe cases, thin shafts with
fractures and bowing deformities (Table 1).
Figure 12. Osteogenesis
imperfecta. (a-c) US images show bone
fractures and deformities.
Note the femoral irregularity and
angulation (arrow in a), a finding that is
consistent with fractures; the decreased
skull ossification, which allows easy
visualization of the intracranial structures
(b); and the irregular shape of the ribs
(arrow in c), a finding that also suggests
fractures. Decreased echogenicity of the
limbs with shortening, decreased
echogenicity of the ribs with fractures, and
hypoechogenicity of the head suggest
osteogenesis imperfecta according to the
diagrams in Figures 5, 6, and 8,
respectively. (d) Postmortem photograph
shows irregular ribs (arrow) due to healing
fractures. (e) Postmortem photograph
shows deformed extremities, findings that
are consistent with fractures.
(f) Postmortem radiograph shows wavy ribs
(black arrow) and irregular deformed long
bones (white arrows) due to multiple
Features of Various Types of Osteogenesis Imperfecta
Generalized demineralization; increased bone fragility,
sometimes with secondary deformities; retarded
ossification of the cranial vault
Generalized demineralization with multiple fractures;
thick, short crumpled shafts of the long bones;
rectangular femora with a wavy appearance; severe
retardation of calvarial bone formation; short, thick
ribs with continuous beading
Generalized osteopenia; short, deformed long tubular bones
with broad metaphyses and thinner di-aphyses; retarded
calvarial ossification; thin ribs with discontinuous
IV/V Generalized demineralization; increased bone fragility,
sometimes with secondary deformities; bowed long bones;
retarded ossification of the cranial vault
•Chondrodysplasia punctata (Fig 13) includes a
varied group of disorders in which there is calcific
stippling of epiphyses, generally identified on
•Rhizomelic chondrodysplasia punctata and a
nonrhizomelic type (Conradi-Hunermann syndrome)
were originally described, with recessive and Xlinked dominant inheritance, respectively, but an Xlinked recessive type exists as well.
•Rhizomelic chondrodysplasia punctata with
autosomal recessive inheritance is due to alterations
in perioxisomal metabolism, whereas the X-linked
dominant type is a result of mutations in the delta 8
sterol isomerase enzyme, resulting in abnormal
•Other forms with different inheritance have also
been described. Findings can include craniofacial
dysmorphism, ocular abnormalities, cutaneous
abnormalities, asymmetric shortening of the
limbs, and joint contractures
•Prognosis is extremely poor, with severe mental
retardation, spastic tetraplegia, and thermoregulatory
•Radiologic features include very short humeri and
relatively short femora with some metaphyseal splaying.
•Punctate calcification of epiphyses at the ends of long
bones is present and may be seen prenatally
•Facial features include a flat face with a small “saddle”
nose. There are multiple contractures.
•Ascites and polyhydramnios have been reported. The
radiologic finding of diffuse epiphyseal calcific
stippling can be seen in a number of inherited and
acquired disorders, such as exposure to drugs
(warfarin, hydantoin); lysosomal, peroxisomal, and
metabolic disorders; and trisomies 18 and 21.
•However, sterol quantification demonstrated an
elevated cholesterol/cholesterol ratio, consistent
with the diagnosis of sterol delta 8 isomerase
deficiency, or chondrodysplasia punctata type 2
(CDPX2) (Conradi-Hunermann syndrome).
Figure 13. Chondrodysplasia punctata. (a) US image shows flattening of
the nose (arrow). (b) US image shows a small head (microcephaly) and
punctate irregular epiphyses in the long bones (arrows). The differential
diagnosis could include spondyloepiphyseal dysplasia,
hypochondroplasia, and chondrodysplasia punctata according to the
diagrams in Figures 4, 7, and 8, respectively. In this case, clinical
correlation and laboratory studies were needed to arrive at the diagnosis
of chondrodysplasia punctata. (c, d) Radiographs show a small head with
a flat face (arrow in c) and stippled epiphyses in the long bones (arrows in
•The term “diastrophic” implies twisting and describes
the twisted habitus in diastrophic dysplasia (Fig 14).
•The mode of inheritance is autosomal recessive due to
mutations in the dia-strophic dysplasia sulfate
transporter gene located at chromosome 5q32-q33.1,
resulting in under sulfated proteoglycans in the cartilage
•Micromelic dwarfism with clubfeet, hand deformities
(abducted or hitchhiker‟s thumb), multiple flexion
contractures, and scoliosis are present.
Figure 14. Diastrophic dysplasia. (a-d) US images show short broad long bones
(calipers in a), hitchhiker’s thumb (arrows in b), bilateral clubfeet (arrowheads in
c), a sloping forehead (arrow in d), and marked micrognathia (arrowhead in d).
According to the diagrams in Figures 2 and 7, the pathognomonic finding of
hitchhiker’s thumb— characterized by flexion at the metacarpophalangeal joint and
hyperextension at the interphalangeal joint—suggests diastrophic dysplasia. (e)
Postmortem photograph shows the bilateral clubfeet with limb shortening (arrowheads)
and bilateral hitchhiker’s thumb (arrow). (f) Postmortem photograph shows the
micrognathia (arrowhead) and sloping forehead (arrow). (g) Radiograph shows the
metaphyseal widening of long bones (double arrows) and irregularity of the metacarpal
and metatarsal bones (single arrow).
•The bones are characterized by crescent-shaped
flattened epiphyses, a short and broad femoral
neck, and shortening and metaphyseal widening
of the tubular bones.
•There is irregular deformity and shortening of the
metacarpal bones, metatarsal bones, and
phalanges, along with abduction of the great toes
•Progressive thoracolumbar kyphoscoliosis,
cervical kyphosis, and irregular deformities of
vertebral bodies are seen.
•In addition, micrognathia and cleft palate are
frequently observed .
Genes That Can Be Screened or Diagnosed In Utero
Multiple epiphyseal dysplasia, pseudoachondroplasia
Ellis-van Creveld syndrome
Osteogenesis imperfecta types I-IV, Ehlers-Danlos
Achondrogenesis type II, hypochondrogenesis, Kniest
dysplasia, spondyloepiphyseal dysplasia,
spondyloepimetaphyseal dysplasia, Stickler dysplasia
Thanatophoric dysplasia types 1 and 2,
hypochondroplasia, other FGFR3 disorders, SADDAN
Diastrophic dysplasia, achondrogenesis type 1B,
atelosteogenesis type II, multiple epiphyseal dysplasia
other diastrophic dysplasia variant disorders
COMP, COL9A1, COL9A2, COL9A3, MATN3
Note.—For a more detailed list of biochemical and molecular tests available for the
diagnosis of skeletal dysplasia, see the University ofWashington-sponsored World Wide
Web page GeneTests (http://www.genetests.org). COL1A1 = collagen, type I, alpha 1; COL1A2 =
collagen, type I, alpha 2; COL2A1 = collagen, type II, alpha 1; COL9A1 = collagen,
type IX, alpha 1; COL9A2 = collagen, type IX, alpha 2; COL9A3 = collagen, type IX,
alpha 3; COMP = cartilage oligomeric matrix protein gene; EVC = Ellis-van Creveld;
DTDST (SLC26A2) = diastrophic dysplasia sulfate transporter (solute carrier family 26
[sulfate transporter] member 2); MATN3 = matrilin 3; RUNX2 = runt-related
transcription factor 2; SADDAN = severe achondroplasia with developmental delay and
•A substantial percentage of fetuses with a skeletal
dysplasia die in utero, are stillborn, die as neonates,
or are delivered after elective termination of
•Establishment of the correct diagnosis of the skeletal
dysplasia will likely require pathologic diagnostic
• Minimal postmortem (autopsy) work-up should
include (a) external examination with photographs;
(b) postmortem whole-body radiographs; and (c)
skin or other tissue biopsy specimens for
chromosome analysis and preservation of
fibroblasts for possible later biochemical,
enzymatic, or genetic studies, to be sent to
specialty laboratories as indicated.
Imaging Approach : Post-natal Skeletal
AP and lateral skull to include the atlas and axis
AP lumbar spine
Lateral thoracolumbar spine
AP one lower limb
AP one upper limb
Postero-anterior (PA) one hand (usually left for
bone age assessment)
In preterm fetuses and stillbirths, babygram i.e. two
anteroposterior (AP) and lateral films from head to
Cone down views also required
Imaging of other family members suspected of
having same condition
What to look for?
A – Anatomical localisation
B – Bones
C – Complications
D – Dead/alive
A- Anatomical site
Cleidocranial dysplasia, ischiopubicpatella syndrome
Spondyloepimetaphyseal dysplasia (tarda or
B – Bones
Bone islands e.g.
Metaphyses – flared
Epiphyses- stippled or cone-shaped
Hooked vertebral bodies as in
Posterior scalloping of vertebral bodies as in
neurofibromatosis and achondroplasia
Sloping acetabular roofs as in
Horizontal trident acetabular roofs seen as in
Trident of the hands in achondroplasia
Short, long, large, broad or hypoplastic
Too many, too few, or fused
Fractures e.g. osteogenesis imperfecta
Atlantoaxial subluxation as in mucopolysaccharidosis
Limb length discrepancies as in Epiphyseal stippling,
Malignancy e.g in Multiple cartilaginous exostoses and
Maffucci‟ s syndrome
•fetal pathologic analysis, although the internal
examination is not as critical as the three items listed in
the preceding paragraph.
• The postnatal work-up should provide essential
diagnostic information for (a) counseling parents for
future pregnancies, including formulating recurrence
risk; and (b) designing strategies for prenatal monitoring
and diagnosis in future pregnancies.
• For example, more than 99% of patients with
achondroplasia have either a GLY380Arg substitution
resulting from point mutation in the FGFR3 gene or a
mutation at nucleotide 1138; hence, a definite
diagnosis is possible in the majority of cases.
• Osteogenesis imperfecta is caused by mutations in
either the COL1A1 or COL1A2 gene, resulting in
abnormal molecular constitution of procollagen
•The diagnosis can be confirmed with biochemical
analysis of collagen or DNA sequencing of COL1A1
and COL1A2 . Some of the genes that can be
screened are listed in Table 2.
Group 1 (Achondroplasia group)
- Bullet-shaped‟ vertebral bodies
- Decrease in interpedicular distance in lumbar spine
- Flat acetabular roofs
- Short wide tubular bones
- Large skull vault, relatively short base & Small
- Relative overgrowth of fibula
- Most common lethal neonatal skeletal dysplasia
- Short ribs with wide costochondral junctions
- Severe platyspondyly
- „telephone receiver femora‟
- „clover leaf skull‟
- Short broad tubular bones in
- the hands feet
Group 3 (Metatropic Dysplasia Group)
Short tubular bones
Flat acetabular roofs
Group 4/Asphyxiating thoracic
with short ribs,
medial and lateral
Asphyxiating thoracic dysplasia
Group 8 (Type II Collagenopathies)
dysplasia congenita &
Characteristic mound of bone in central
and posterior part of the vertebral end
Group 11 (Multiple Epiphyseal
Dysplasias And Pseudoachondroplasia
Short limbs with
normal head and face
protrusion of the
vertebral end plates
Group 12 (Chondrodysplasia
around the joints
and in laryngeal
Group 13 (Metaphyseal Dysplasias)
- Metaphyseal flaring
- Increased density
and unevenness of
particularly of upper
femora and around
Group 19 (Dysplasias With Predominant
Membranous Bone Involvement)
Group 22 (Dysostosis Multiplex)
Thick vault with
Ovoid, hookshaped vertebral
Morquio's Syndrome (MPS-IV)
Group 24 (Dysplasias With Decreased
- a group of conditions sec. to abnormality of Type
- Type I-IV
- Most severe Type II & III
- Mildest Type I
Group 26 (Increased Bone Density
Without Modification Of Bone Shape)
- Alternating bands
- Sclerotic foci
Group 31 (Disorganized Development
Of Cartilaginous And Fibrous
Components Of The Skeleton)
Multiple cartilaginous exostoses
- Multiple flat or protuberant exostoses
- Short ulna distally (reverse Madelung
- Expansion of
- Areas of
- Skull - asymmetrical thickening of the
vault with sclerosis at base: multiple
rounded areas of radiolucency
Obliteration of the paranasal air sinuses
Obliteration of the paranasal air sinuses
„Ground-glass‟ areas in alteration with
patchy sclerosis and expansion
Cortical thinning and endosteal scalloping
Radiation load to fetus
Low-dose fetal CT, NEVER first trimester
Radiation dose: varies according to
Mean radiation dose: 4.8 mSv
Up to 50 mSv is “negligible”
100 mSv, threshold for fetal damage