Volume 21

Congenital Defects (Part 2)

Mucopolysacharidoses

Diastrophic dwarfism

Tarsal epiphyseal aclasia

Achondroplasia

Hypochondroplasia

Achondrogenesis & Thanatophoric dwarfism

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

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.

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

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.

Case #1 Hurler’s

Mentally retarded child with bushy eyebrows, depressed nasion

puffy lips, hydrocephali and coxa valgum

At age 3.5 yrs we see a typical slipper defect of L-2 along with

other spondyloepiphyseal defects of spine and extremities

Costochondral rib biopsy showing gargoyle foam cells in

cartilage, periosteal fibroblasts and marrow tissue

Case #2 Hurler’s

6 yr mentally retarded male

with puffy lips and large tongue,

hydrocephali, enlarged cella

tersica and coxa valgum

Classic slipper defect of L-2 and flexion deformity of fingers

(campnodactyly) and tapered proximal metacarpals

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

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.

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

SED deformity with LD platyspondyly, horizontal paddle ribs,

wine shaped pelvic inlet and coxa varum hip defects

Case #2 Morquio’s

Typical epiphyseal deformities with knocked knees in Morquio’s

Case #3 Morquio’s

Age 7 8 yrs

18 yrs

Severe coxa varum epiphyseal deformity over 11 yrs of growth

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.

Diastrophic Dwarfism

Young boy with SED deformity similar to Morquio’s but with

severe major joint dislocation and club feet

Case #1

Plataspondyly of cervical spine,

mid dorsal scoliosis and

dislocated hips

Normal appearing head and face except for the cauliflower ear

Dislocated elbow,

thumb, & knee with

short long bones 2nd

to epiphyseal

hypoplasia

Campnodactyly of

fingers & hitch-

hiker’s deformity

of thumbs

Resistant club feet

and short toes

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.

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

Case #2 Trevor’s of Hip & Knee

20 mo female with varus knee 2nd to Trevor’s of knee & hip

Case #3 Tarsal Epiphyseal Aclasia

Teen aged boy with pseudo osteochondroma medial malleolus

resected and surgical specimen seen to your right

Case #4 Tarsal Epiphyseal Aclasia

4 yr old male with none tender lump posterior lateral to ankle

thought to be an osteochondroma

Case #5 Tarsal Epiphyseal Aclasia

6 yr male with progressive painless enlargement and stiffness

of ankle and subtalar joint for 2 yrs

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

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.

Case #1 Achondroplasia

Young achondroplastic boy with mild hydrocephali, a flat chest,

rhizomelic short limbs, kyphotic L-2 vertebral body & short ribs

Mild hydrocephali and depressed nasion

X-ray of pelvis shows the

champagne glass defect with

squarred off iliac crests.

Note short femur with strong

cortical bone and normal

epiphyses

Short strong fingers &

classic trident hand

Case #2 Achondroplasia

Rhizomelic short limbs and normal appearing trunk

Normal skull compared to that

of an achondroblastic with

severe stenosis of the foramen

magnum

Stenosis of LS vertebral canal

resulting in cauda equina

syndrome

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”.

Case #1 Hypochondroplasia

Young adult male with mild

rhizomelic shortening of the

extremities and stenosis of

the LS spine

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.

Case #1 Thanatophoric Dwarf

Still born infant with short limbs, hydrocephali and short ribs

X-ray of pelvis and short

lower extremities

X-ray of short upper

extremities and short ribs

Macrosection of entire femur obtained at autopsy

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”.

Case #1 Achondrogenesis

Still born infant with short limbs, deficient bone in hands &

feet, skull and ribs plus generalized body edema