1. 1

2. Definitions
 Osteochondrodysplasias:
- Abnormalities of bone and/or cartilage growth
- Because of abnormal gene expression,
phenotypes continue to evolve throughout
lifespan
 Dysostoses :
- Altered blastogenesis in first 6 weeks of IU life
- Phenotype fixed
2

3. •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
throughout life.

4. •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
overlapping
features,
lack of precise molecular diagnosis for
many
disorders

5. Lack of a systematic approach
the inability of ultrasonography (US) to provide
an integrated view,
variability in the time at which findings
manifest
in some skeletal dysplasias.

6. •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
detectable
identified.
at
two
dimensional
US
may
be

7. •The radiologist plays a major role in making an
accurate diagnosis; however, representatives of other
disciplines, including clinicians, molecular biologists,
and
pathologists,
can
also
provide
important
diagnostic information.
•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.

8. • 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.

9. •This nomenclature was modified in 1983, 1997, and
2001. The major change in 2001 was the addition of
genetic dysostoses-osteochon-drodysplasias.
• Dysostoses occur singly or in combination.
•Skeletal
dysplasias
are
caused
by
widespread
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

10.  International Classification of
Osteochondrodysplasias, published in 2002
 Classified1. Osteochondrodysplasias - 33 groups (Groups
1–33)
2. Dysostoses – 3 (Groups A–C)
- A - predominantly craniofacial involvement
- B - predominant axial involvement
- C - predominant involvement of hands & feet
10

11. •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
maternal-fetal
medicine
specialists
and
radiologists.
• The prevalence of skeletal dysplasias (excluding
limb amputations) is estimated at 2.4 per 10,000
births.

12. • 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.

13. • 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
dysplasias.

14. •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
been observed.

15. •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.

16. •US is the primary method for imaging a fetus.

17. •US technique for assessing fetal skeletal dysplasia;
•discuss and illustrate the US diagnosis of skeletal
dysplasias such as
 limb deficiency,
thanatophoric dysplasia,
 osteogenesis imperfecta,
chondrodysplasia punctata, and
diastrophic dysplasia; and
•briefly review postnatal evaluation in affected
patients.

18. Imaging Approach : Antenatal US
 Long Bones:
- Long bones lengths
- Absence and malformation
- Hypoplasia : Rhizomelia, Mesomelia, Rhizo-
mesomelia, Acromelia
- 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)
18

19. Long Bones
•The long bones in all of the extremities should be
measured.
•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.

20. •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.

21. 21

22. Femur Length

22

23. Thorax
•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
pulmonary hypoplasia.

24. •Other parameters used are a chest
circumference-abdominal circumference
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 .

25. •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 .

26. •The shape and integrity of the thorax should be
noted. Abnormal rib size and configuration are
also seen in patients with lethal skeletal
dysplasias.
•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
dysplasia.

27. Chest
 Chest–trunk length ratio less than 0.32
 Femur length–abdominal circumference ratio less
than 0.16
 Hypoplastic thorax occurs in – lethal dysplasia, e.g.
thanatophoric dysplasia, achondrogenesis,
osteogenesis imperfecta.
27

28. 28

29. 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
deformities.

30. Ultrasound Clinodactyly, right hand Hypoplastic middle
phalanx in the right 5th finger indicated by the arrow.

31. Syndactyly “mitten hand”
Apert syndrome: acrocephalosyndactyly

32. • 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.

33. Hitchhiker thumb
Second-Trimester Sonographic Diagnosis of
Diastrophic Dysplasia.

34. Hands and Feet
 Pre- or postaxial polydactyly
 Syndactyly
 Clinodactyly
34

35. The Hitchhiker's Thumb consists of :
•Oval and hypoplastic first metacarpal.
•Abducted proximally positioned thumb.
•Low set first digit.
•Etiology:
1.Skeletal dysplasia • Diastrophic dysplasia.
•Campomelic dysplasia.
2.Isolated and familial (15%).
3.Trisomy 18 (30%) and trisomy 13.
4.Fetal akinesia and arthrogryposis.
5.Prolonged oligohydramnios.
6.Limb-body wall complex (32%).
7.Spina-bifida.

36. rocker-bottom foot
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

37. 37

38. Skull
•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

39. •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.

40.  The inter-ocular distance (IOD) is a measurement between
the two medial canthi of each eye
40

41. Spine
•The spine should be carefully imaged to assess the
relative total length and the presence of curvature to
exclude scoliosis.
•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

42. Spine and Pelvis
 Platyspondyly
42

43. Pelvis
•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.

44. •Pelvic shape may be difficult to evaluate at
routine US, and three dimensional (3D) US may
be necessary.
• 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 .

45. RG ■ Volume 28 • Number 4
Long bones -
Dighe et al 1063
All long bones to be measured
Measurement
Bones
Mineralization
Curvature
Fractures
(mm)
Standard measurement for wks
Femur
Right
Left
Tibia
Right
Left
Fibula
Right
Left
Humerus
Right
Left
Ulna
Right
Left
Radius
Right
Left
Bones
Absent
Hypoplastic
Any malformation
Thorax
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
Clavicle
Measurement
Normal
measurement of clavicles at wks
Clavicles
Right
Left
Hands and feet Foot
measurement
Shape of thorax Bell Shaped - Yes / No
Chest circumference
Measurement
Normal
Preaxial Postaxial
Syndactyly Yes /No Postural
deformities
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
Foot
Femur/foot ratio
Spine
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
Decreased
Vertebral Height - Normal / Decreased
Biorbital diameter - Distance between the inner margins of the orbits
Measurement
Normal measurement of biorbital diameter at_ wks
Biorbital diameter
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
dysplasia.

46. Diagnosis with US
If the limbs are disproportional (Figs 2-5), the
following questions should be addressed:
1. Does the abnormality affect the proximal
(rhizomelic),
middle (mesomelic), or distal
(acromelic) segment?
2. Is polydactyly, ectrodactyly, clinodactyly, or
syndactyly present?
3. Are there any fractures, curved bones, or joint
deformities, or clubbing of the foot or hand?

47. 4. Are metaphyseal changes present?
5. Is there a premature appearance of ossification
centers?
6. Are there any hypoplastic or absent bones?

49. Figure 3. Diagram illustrates a diagnostic algorithm for
use in fetuses with moderate limb shortening and
normal mineralization. OI = osteogenesis imperfecta.

50. 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.

51. Figure
5.
Diagram
illustrates
a
diagnostic
algorithm for use in fetuses with normal or
shortened limbs and decreased mineralization. OI
= osteogenesis imperfecta.

52. If the spine is mainly affected, one should ask the
following questions:
1.Is the spine short because of missing parts (eg,
sacral
agenesis)?
2. Is there abnormal curvature?
3. Is there shortening of vertebral bodies?

53. 4. Are all parts of the spine equally affected
(eg, achondrogenesis)?
5. Is platyspondyly present (thanatophoric
dysplasia)?
6. Is the spinal canal of normal width?
7. Are any meningomyeloceles present?

54. If the thorax is mainly affected (Fig 6), the following
questions should be addressed:
1. Is the thorax extremely small (thanatophoric
dysplasia)?
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
II)?

55. 5. Is there clavicular aplasia, hypoplasia, or
partitioning
(cleidocranial dysostosis)?
6. Is the scapula normal or abnormal (camp-tomelic
dysplasia)?
7. Are there any gaps between ribs (Jarcho-Levine
syndrome)?

56. Figure 6. Diagram illustrates a diagnostic algorithm for use in
fetuses
with
suspected
skeletal
dysplasia
abnormalities. OI = osteogenesis imperfecta.
and
thoracic

57. Additional findings include external anomalies
(abnormally shaped ears, caudal appendage), facial
deformities (cleft palate, micrognathia, short nasal
bridge [Fig 7]), internal anomalies (eg, cardiac
anomalies [Ellis-van Creveld syndrome]), urinary tract
abnormalities (short-rib poly dactyly type 2), genital
abnormalities (Robert syndrome, camptomelic dysplasia
[ambiguous genitalia]); gastrointestinal tract
abnormalities (achondrogenesis type 1), and skull
abnormalities (asymmetry, basilar invagination,
cloverleaf skull, craniosynostosis, defective

58. Figure 7. Diagram illustrates a diagnostic algorithm for use in
fetuses
with
suspected
skeletal
dysplasia
abnormalities. OI = osteogenesis imperfecta.
and
facial

59. Figure 8. Diagram illustrates a diagnostic algorithm for
use in fetuses with suspected skeletal dysplasia and
skull abnormalities. OI = osteogenesis imperfecta.

60. Examples of Fetal Skeletal Dysplasia
Limb Deficiency
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
craniofacial structures.

61. •Isolated extremity amputation can be due to amniotic
band syndrome, exposure to a teratogen, or vascular
accident .
•In most cases, the anomaly is sporadic, and risk of
recurrence is negligible.

62. 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.

63. •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

64. •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.

65. Thanatophoric Dysplasia
•The term “thanatophoric dysplasia” is derived from
the Greek word thanatophoros, which means “bearing
death.”
•Thanatophoric dysplasia is themost common lethal
skeletal dysplasia. Langer et al separated this
condition into two types: type 1 (Fig 10) and type 2
(Fig 11).

66. •Both types are caused by mutations of the geneencoding fibroblast growth factor receptor 3
(FGFR3).
• 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

67. •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 .

68. •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
cases.
•Death occurs in early infancy in the majority of
cases due to respiratory insufficiency from

69. d.
e.
f.
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).

70. 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).

71. Osteogenesis Imperfecta
•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

72. •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 .

73. •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.

74. • 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.

75. •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).

76. 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
fractures.

77. Table 1
Features of Various Types of Osteogenesis Imperfecta
Type
I
Description
Generalized demineralization; increased bone fragility,
sometimes with secondary deformities; retarded
ossification of the cranial vault
II*
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
III
Generalized osteopenia; short, deformed long tubular bones
with broad metaphyses and thinner di-aphyses; retarded
calvarial ossification; thin ribs with discontinuous
fractures
IV/V Generalized demineralization; increased bone fragility,
sometimes with secondary deformities; bowed long bones;
retarded ossification of the cranial vault
*Perinatal lethal.

78. Chondrodysplasia Punctata
•Chondrodysplasia punctata (Fig 13) includes a
varied group of disorders in which there is calcific
stippling of epiphyses, generally identified on
conventional radiographs.
•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.

79. •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
cholesterol biosynthesis.

80. •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

81. •Prognosis is extremely poor, with severe mental
retardation, spastic tetraplegia, and thermoregulatory
instability.
•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

82. •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.

83. •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).

84. 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
d).

85. Diastrophic Dysplasia
•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
matrix .

86. •Micromelic dwarfism with clubfeet, hand deformities
(abducted or hitchhiker‟s thumb), multiple flexion
contractures, and scoliosis are present.

87. 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).

88. •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
and clubfeet.

89. •Progressive thoracolumbar kyphoscoliosis,
cervical kyphosis, and irregular deformities of
vertebral bodies are seen.
•In addition, micrognathia and cleft palate are
frequently observed .

90. Table 2
Genes That Can Be Screened or Diagnosed In Utero
Disease Entities
Multiple epiphyseal dysplasia, pseudoachondroplasia
Ellis-van Creveld syndrome
Osteogenesis imperfecta types I-IV, Ehlers-Danlos
syndrome
Achondrogenesis type II, hypochondrogenesis, Kniest
dysplasia, spondyloepiphyseal dysplasia,
spondyloepimetaphyseal dysplasia, Stickler dysplasia
Thanatophoric dysplasia types 1 and 2,
achondroplasia,
hypochondroplasia, other FGFR3 disorders, SADDAN
dysplasia
Diastrophic dysplasia, achondrogenesis type 1B,
atelosteogenesis type II, multiple epiphyseal dysplasia
(recessive),
other diastrophic dysplasia variant disorders
Cleidocranial dysplasia
Genes
COMP, COL9A1, COL9A2, COL9A3, MATN3
EVC
COL1A1, COL1A2
COL2A1
FGFR3
DTDST (SLC26A2)
RUNX2
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
acanthosis nigricans.

91. Postnatal Evaluation
•A substantial percentage of fetuses with a skeletal
dysplasia die in utero, are stillborn, die as neonates,
or are delivered after elective termination of
pregnancy.
•Establishment of the correct diagnosis of the skeletal
dysplasia will likely require pathologic diagnostic
work-up.

92. • 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.

93. Imaging Approach : Post-natal Skeletal
Survey
 AP and lateral skull to include the atlas and axis
 AP chest
 AP pelvis
 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)
93

94. Modifications
 In preterm fetuses and stillbirths, babygram i.e. two
anteroposterior (AP) and lateral films from head to
foot
 Cone down views also required
 Imaging of other family members suspected of
having same condition
94

95. What to look for?
 A – Anatomical localisation
 B – Bones
 C – Complications
 D – Dead/alive
95

96. A- Anatomical site
 Cleidocranial dysplasia, ischiopubicpatella syndrome
 Spondyloepimetaphyseal dysplasia (tarda or
congenita)
 Metaphyseal chondrodysplasia
96

97. B – Bones
 Structure
 Shape
 Size
 Sum
 Soft tissues
97

98. Structure
 Bone density
 Exostoses and
enchondromas
 Metaphyseal striations-
osteopathia striata
 Bone islands e.g.
osteopoikilosis
98

99. 99

100. Shape








Metaphyses – flared
Epiphyses- stippled or cone-shaped
Platyspondyly
Hooked vertebral bodies as in
mucopolysaccharidoses
Posterior scalloping of vertebral bodies as in
neurofibromatosis and achondroplasia
Sloping acetabular roofs as in
mucopolysaccharidoses
Horizontal trident acetabular roofs seen as in
achondroplasia
Trident of the hands in achondroplasia
100

101. Flared Metaphyses
Stippled Epiphyses
Hooked vertebral bodies
101

102. Size
 Short, long, large, broad or hypoplastic
Sum
 Too many, too few, or fused
Complications
 Fractures e.g. osteogenesis imperfecta
 Atlantoaxial subluxation as in mucopolysaccharidosis
 Progressive scoliosis
 Limb length discrepancies as in Epiphyseal stippling,
dysplasia epiphysealis
 Malignancy e.g in Multiple cartilaginous exostoses and
Maffucci‟ s syndrome
102

103. Fractures
Atlantoaxial instability
103

104. •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.

105. • 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.

106. • Osteogenesis imperfecta is caused by mutations in
either the COL1A1 or COL1A2 gene, resulting in
abnormal molecular constitution of procollagen
type I.
•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.

107. Group 1 (Achondroplasia group)
Achondroplasia :
- Bullet-shaped‟ vertebral bodies
- Decrease in interpedicular distance in lumbar spine
caudally
- Flat acetabular roofs
- Short wide tubular bones
- Large skull vault, relatively short base & Small
foramen magnum
- Relative overgrowth of fibula
107

108. 108

109. Group 1
 Thanatophoric dysplasia
- 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
109

110. Group 3 (Metatropic Dysplasia Group)
 Short tubular bones
with marked
metaphyseal widening
(dumb-bell)
 Platyspondyly,
Progressive
kyphoscoliosis
 Large intervertebral
discs
 Flat acetabular roofs
110

111. Group 4/Asphyxiating thoracic
dysplasia
•Small thorax
with short ribs,
horizontally
orientated
•Horizontal
acetabula with
medial and lateral
„spurs‟ (trident)
Asphyxiating thoracic dysplasia
111

112. Group 8 (Type II Collagenopathies)
 Spondyloepiphyseal
dysplasia congenita &
Tarda
Characteristic mound of bone in central
and posterior part of the vertebral end
plates
112

113. Group 11 (Multiple Epiphyseal
Dysplasias And Pseudoachondroplasia
 Short limbs with
normal head and face
 Platyspondyly with
tongue-like anterior
protrusion of the
vertebral bodies
 Biconvex
configuration of
vertebral end plates
 Irregular
metaphyses
113

114. Group 12 (Chondrodysplasia
Punctata/Stippled Epiphyses)
 Stippled
calcification in
cartilage,
particularly
around the joints
and in laryngeal
and tracheal
cartilages
114

115. Group 13 (Metaphyseal Dysplasias)
 Metaphyseal
chondrodysplasia
(Schmid)
- Metaphyseal flaring
- Increased density
and unevenness of
metaphyses,
particularly of upper
femora and around
knees
115

116. Group 19 (Dysplasias With Predominant
Membranous Bone Involvement)
 Cleidocranial
dysplasia
116

117. Group 22 (Dysostosis Multiplex)
 Mucopolysacchari
-
-
doses
Macrocephaly
Thick vault with
„ground-glass
capacity‟
„J‟-shaped sella
Ovoid, hookshaped vertebral
bodies with
thoracolumbar
gibbus
117

118. Morquio's Syndrome (MPS-IV)
 Normal intelligence
 Absent odontoid
peg
 Platyspondyly
 Progressive
disappearance of
femoral capital
epiphyses
118

119. Group 24 (Dysplasias With Decreased
Bone Density)
 Osteogenesis imperfecta
- a group of conditions sec. to abnormality of Type
1 collagen
- Type I-IV
- Most severe Type II & III
- Mildest Type I
119

120.  Wormian bones
 Basilar




invagination
Hyperplastic
callus
Severe protrusio
acetabuli
„Codfish‟ vertebral
bodies
„Tam O'Shanter‟
appearance
120

121. Group 26 (Increased Bone Density
Without Modification Of Bone Shape)
 Osteopetrosis
- Generalized
increase in
skeletal density
- Alternating bands
of radiolucency
and sclerosis
121

122.  Osteopoikilosis
- Sclerotic foci
(islands), around
pelvis and
metaphyses of
long bones
122

123. 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
deformity)
123

124. Diaphysial Aclasis
124

125.  Enchondrom
atoses
(Ollier's
disease/
Maffuci
syndrome)
- Expansion of
the bone
with cortical
thinning
- Areas of
calcification
within the
lesions
125

126.  Fibrous dysplasia
- 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
126

127. 127

128. Prenatal CT as a tool for dx of severe skeletal
abnormalities
128

129. How to
CONSENT
 Mark with US the top and bottom of the uterus
 Image ONLY what is strictly necessary
 Topogram
 kVp: 80-100
 Actual scan-few seconds.
 No contrast.
129

130. 130

131. Radiation load to fetus
Low-dose fetal CT, NEVER first trimester
 Radiation dose: varies according to
maternal size
 Mean radiation dose: 4.8 mSv

Up to 50 mSv is “negligible”
 100 mSv, threshold for fetal damage
131

132. Thanatophoric dysplasia
132

133. Oseogenesis imperfecta
133

134. THANK YOU.
134