The document discusses several types of congenital skeletal defects including mucopolysaccharidoses (MPS), diastrophic dwarfism, Trevor's disease, achondroplasia, hypochondroplasia, thanatophoric dwarfism, and achondrogenesis. It provides details on the genetic causes, characteristic bone abnormalities, and clinical features of each condition based on patient cases. Radiographic images are included to illustrate the skeletal abnormalities.

1. Volume 21
Congenital Defects (Part 2)
Mucopolysacharidoses
Diastrophic dwarfism
Tarsal epiphyseal aclasia
 Achondroplasia
 Hypochondroplasia
 Achondrogenesis & Thanatophoric dwarfism

2. Mucopolysaccharidoses (MPS)
(Dysostosis Multiplex)
The MPS dwarfs are the result of a familial genetic defect in
which there is a deficient enzyme system that normally breaks
down the acid mucopolysaccharides in the cytoplasm of
mesenchyme cells including fibroblasts, chondroblasts and osteo-
blasts. MPS inclusion bodies can be seen in these cells and acid
mucopolysaccharides will be found in the urine of these dwarfs.
The bony abnormalities seen early in childhood are similar to
those seen in SED congenita with short limbs and spines with
kyphotic deformities. Soft tissue involvement can include
enlarged livers and spleens and clouded corneas. Mental retard-
ation can result from CNS involvement. Early death can result
from coronary artery occlusions and heart failure.
The Mucolipidoses (ML) are dwarfs with a similar
enzymatic defect that prevent the catabolism of mucolipids in

3. mesenchyme cells resulting in the formation of inclusion bodies
seen in the cytoplasm of the various connective tissue cells.
In the following slide we see a listing of all the MPS and ML
conditions with the various eponyms, enzymatic defects and
clinical features of each one of these various conditions.

5. Hurler’s Syndrome (MPS 1-H)
(Gargoylism)
Of all the MPS’s, Hurler’s and Morquio’s have the greatest
skeletal abnormalities with short limbs and trunk. Hurler’s is an
autosomal recessive disorder which becomes manifest in the first
few years of life. They are SED congenita type dwarfs with
distinctive facies, mental retardation, deafness, corneal opacities,
hepatosplenomegaly, cardiomegaly resulting in heart failure that
frequently results in death in the first decade of life. Dermatan
sulfate and heparin sulfate are the acid mucuopolysacchrides
found in the urine and the enzymatic defect in Hurler’s is alpha-
L-iduronidase. MPS occlusion of the normal outlet of cerebral
fluid from the brain results in hydrocephaly and a characteristic
boot shaped cella turcica. The universal plataspondyly of the
entire spine results in LD kyphosis and atlantoaxial subluxation.
We see long bone shortening with epiphyseal defects seen in

6. MED dwarfs with coxa valgus deformity of the hip contrasting
the coxa vara defect seen in Morquio’s. In hand x-rays we see
shortened bullet shaped phalanges with short metacarpals and
metatarsals with tapering at the base of the short bones.

7. Case #1 Hurler’s
Mentally retarded child with bushy eyebrows, depressed nasion
puffy lips, hydrocephali and coxa valgum

8. At age 3.5 yrs we see a typical slipper defect of L-2 along with
other spondyloepiphyseal defects of spine and extremities

9. Costochondral rib biopsy showing gargoyle foam cells in
cartilage, periosteal fibroblasts and marrow tissue

10. Case #2 Hurler’s
6 yr mentally retarded male
with puffy lips and large tongue,
hydrocephali, enlarged cella
tersica and coxa valgum

11. Classic slipper defect of L-2 and flexion deformity of fingers
(campnodactyly) and tapered proximal metacarpals

12. Case #3 Hurler’s
6 year old child with Hurler’s syndrome with classic hand
deformity and scaphoid (keel shaped) skull due to early closure
of mid sagittal suture line and coxa varum deformity of the prox.
humeral epiphyses and paddle shaped ribs

13. Morquio’s (MPS IV)
In Morquio’s we find keratin sulfate in the urine and the
enzymatic defect is galactosamine-6-sulfate sulfatase. As
compared to Hurler’s the face and skull are quite normal, but
the major problem is with spinal shortening with LD kypho-
scoliosis and anterior bulging of the sternum. Odontoid hypo-
plasia can result in C 1 on 2 subluxation and quadriplegia.
The long bones of the extremities are shortened with flattened
and deformed epiphyses as seen in MED. Coxa varum is seen
in the hip compared to the coxa valgum defect in Hurler’s. The
short bones of the hand and feet are the same as we see in
Hurler’s. Corneal clouding and deafness can be seen as in
Hurler’s but Morquio’s patients have normal intelligence and a
variable life span. Cardiac enlargement can result from aortic
valve deficiency.

14. Case #1 Morquio’s
This young boy was normal at birth but developed spinal
shortening at age 2 yrs and keratin sulfate was noted in urine

15. SED deformity with LD platyspondyly, horizontal paddle ribs,
wine shaped pelvic inlet and coxa varum hip defects

16. Case #2 Morquio’s
Typical epiphyseal deformities with knocked knees in Morquio’s

17. Case #3 Morquio’s
Age 7 8 yrs
18 yrs
Severe coxa varum epiphyseal deformity over 11 yrs of growth

18. Diastrophic Dwarfism
(Twisted or Crooked Dwarf)
Diastrophic dwarfs are similar to Morquio’s syndrome as far as
the spondyloepiphyseal deformity seen radiologicially but with
an additional collagen deficiency of the entire musculoskeletel
system resulting in severe ligamentous laxity leading to dis-
located joints, kyphoscoliosis and resistant club foot deformity.
the limbs are shortened because of retarded epiphyseal
ossification centers that are deformed and flatened with growth.
The thumbs and great toes are deformed and held in a hitch-
hiker’s position. Collagen deficient ears result in a typical
cauliflower deformity. Diastrophic dwarfs are autosomal
recessive.

19. Case #1 Diastrophic Dwarfism
Young boy with SED deformity similar to Morquio’s but with
severe major joint dislocation and club feet

20. Plataspondyly of cervical spine,
mid dorsal scoliosis and
dislocated hips

21. Normal appearing head and face except for the cauliflower ear

22. Dislocated elbow,
thumb, & knee with
short long bones 2nd
to epiphyseal
hypoplasia

23. Campnodactyly of
fingers & hitch-
hiker’s deformity
of thumbs
Resistant club feet
and short toes

24. Dysplasia Epiphysealis Hemimelica
Tarsal Epiphyseal Aclasia
(Trevor’s Disease)
Trevor’s disease is a rare epiphyseal dysplasia that results in
overgrowth of the epiphyseal cartilage in young children seen
usually in the lower extremity and on the medial side in males
three times more common then females.The talus is commonly
involved resulting in the term tarsal epiphyseal aclasia. It affects
one side of the body and is rare in the upper extremity. Multiple
bones are involved in a single extremity in 65% of cases. Radio-
graphically the epiphyseal overgrowth takes on the appearance
of an epiphyseal osteochondroma except for the dystrophic
calcification seen in the cartilagenous cap not seen in a true
meataphyseal osteochondroma. If the diagnosis is established
early in childhood the excess hypertrophic epiphyseal cartilage
can be shaved down to match the opposite side of the same
epiphyses before the cartilage converts to subchondral bone.

25. Case #1 Trevor’s Disease Knee
6 yr male with progressive
valgus deformity of knee
with enlarged medial femoral
condyle with dystrophic
calcification treated with
cartilage shaving and results
seen 5 yrs later & no valgus

26. Case #2 Trevor’s of Hip & Knee
20 mo female with varus knee 2nd to Trevor’s of knee & hip

27. Case #3 Tarsal Epiphyseal Aclasia
Teen aged boy with pseudo osteochondroma medial malleolus
resected and surgical specimen seen to your right

28. Case #4 Tarsal Epiphyseal Aclasia
4 yr old male with none tender lump posterior lateral to ankle
thought to be an osteochondroma

29. Case #5 Tarsal Epiphyseal Aclasia
6 yr male with progressive painless enlargement and stiffness
of ankle and subtalar joint for 2 yrs

30. Achondroplasia
The achondroplastic dwarf is a common autosomal dominient
familial condition resulting from a deficiency of central inter-
sticial embryonic cartilage of the growth plate with severe
shortening of the limbs especially at their proximal ends
(rhizomelic). The epiphyses are normal and the peripheral
appositional portion of the intersticial cartilage grows laterally
as a collar around the epiphyseal ossification center creating a
ball-in-socket appearance on x-ray examination. Hypoplasia at
the base of the skull results in a low grade hydrocephali but
rarely results in mental retardation. Hypoplasia of the middle
third of the facial bones results in a depressed nasion. The spine
is normal except for a mild lumbo-dorsal kyphosis and a spinal
stenosis in the lumbosacral area that can result in cauda equina
compression at a young adult age. The major difference between
the severe epiphyseal dysplasitic dwarfs (pseudo achondro-
plastic) and achondroplastic dwarfs is that achondroplastic

31. dwarfs have strong but short long bones with normal epiphyses
that result in normal joint surfaces that do not develop early
osteoarthritis as we see in the epiphyseal dysplastic dwarfs.

32. Case #1 Achondroplasia
Young achondroplastic boy with mild hydrocephali, a flat chest,
rhizomelic short limbs, kyphotic L-2 vertebral body & short ribs

33. Mild hydrocephali and depressed nasion

34. Short strong fingers &
classic trident hand
X-ray of pelvis shows the
champagne glass defect with
squarred off iliac crests.
Note short femur with strong
cortical bone and normal
epiphyses

35. Case #2 Achondroplasia
Rhizomelic short limbs and normal appearing trunk

36. Stenosis of LS vertebral canal
resulting in cauda equina
syndrome
Normal skull compared to that
of an achondroblastic with
severe stenosis of the foramen
magnum

37. Hypochondroplasia
Hypochondroplasia is an autosomal dominant disorder that
becomes evident later in childhood compared to achondroplasia
that is dwarfted at birth. The head and face appear normal but
spinal stenosis is seen in the lumbosacral spine that can cause
neurologic problems requiring surgery. Mild rhizomelic short-
ening of long bones results in an average adult height of 4’8”.

38. Hypochondroplasia
Case #1
Young adult male with mild
rhizomelic shortening of the
extremities and stenosis of
the LS spine

39. Thanatophoric Dwarfism
(death bearing dwarf)
Thanatophoric dwarfism is a very severe variant of achondro-
plasia which is usually a dominant new mutation. These dwarfs
are frequently still born because of severe hydrocephali resulting
in brain damage at birth. Or if they survive birth they frequently
die soon after because of severe shortening of the ribs resulting
in fatal respiratory problems.

40. Case #1 Thanatophoric Dwarf
Still born infant with short limbs, hydrocephali and short ribs

41. X-ray of short upper
extremities and short ribs
X-ray of pelvis and short
lower extremities

42. Macrosection of entire femur obtained at autopsy

43. Achondrogenesis
Achondrogenesis is another very severe variant of achondro-
plasia which is autosomal recessive and frequently are still born
or die shortly there after. The limbs are very short with severe
hypoplasia of the hand and foot bones. There is a generalized
edema of the entire body resulting in the term “monster child”.

44. Case #1 Achondrogenesis
Still born infant with short limbs, deficient bone in hands &
feet, skull and ribs plus generalized body edema