SKELETAL DYSPLASIAS

-Dr.ANKIT BENIWAL

Cleidocranial dysplaisa (cleidocranial dysostosis)

• It is a benign hereditary condition inherited as autosomal

dominant disorder but upto 30% of cases are due to

spontaneous mutation.

• Characterised by incomplete intramembranous

ossification of midline skeletal structures.

Clinical features:

• Large head, with large fontanelles with delayed closure

• Broad mandible

• Supernumerary teeth

• High arched palate.

• Neonatal distress due to thorax being narrowed and bell

shaped

• Excessively mobile shoulders

• May have genu valgum and short fingers

Radiological features

Clavicles

• There may be total (in 10% of cases) or partial absence of

the clavicle.

• The outer end is absent more frequently than the inner.

• Central defects also occur.

• The clavicles may also be normal.

• The scapulae tend to be small and high, and the glenoid

fossae are small

Here we can see absent lateral ends of clavicles (right>left)

Thorax

• The thorax is usually narrow.

• The ribs are short and directed obliquely downward.

• Respiratory distress may occur in the newborn.

• The sternum is incompletely ossified.

• Failure of fusion of neural arches occurs, with delay in

maturation of vertebral bodies, which retain an infantile

biconvex shape.

• Supernumerary or bifid ribs also occur

1. Hypoplasia of bilateral clavicles with symmetric absence of bilateral distal clavicles.2. Somewhat bell-shaped thorcic cavity

Skull

• Skull In the newborn, mincralisation is delayed.

• The facial bones are small but the mandible is normal in size.

• The fontanelles remain open late and the sutures are

widened.

• The bodies of the spheroids are hypoplastic.

• Many wormian bones are seen and frontal and parietal

bossing may be present.

Multiple mosaic accessory bone plates along sagittal and bilateral lambdoid sutures with somewhat symmetric distribution, representing multiple wormian bones.

Mandible appears normal.

Small size of bilateral maxillary sinuses and undevelopment of frontal and sphenoid sinuses s/o hypoplasia of facial bones.

Multiple wormian bones are seen too.

Supernumerary teeth within maxilla with irregular arrangemen.t

Pelvis• Delayed and

imperfect ossification of the pubic bones is a recognised finding and congenital coxa vara is frequently

Hand

• Hands Anomalies of the hand are

very common.

• The second and fifth metacarpals

are long and have supernumerary

ossification centres at their bases.

• The middle phalanges of the second

and fifth phalanges are short.

• Cone epiphyses and distal

phalangeal tapering are found.

Pyknodysostosis• It is a rare autosomal recessive bone dysplasia, characterised

by osteosclerosis and short stature.

• It is a lysosomal disorder due to genetic deficiency in

Cathepsin K.

• Confused with cleidocranial dysplasia because of some similar

clavicular and skull changes. But in this patient is short

statured i.e. below 150cm/5feet.

Clinical features:

1. Short stature, particularly limbs.

2. Delayed closure of cranial sutures.

3. Frontal and occipital bossing.

4. Short broad hands and hypoplasia of nails.

5. Multiple long bone fractures following minimal trauma.

Skull

• There is brachycephaly with wide sutures and persistence of

open fontanelles into adult life.

• Wormian bones are seen.

• The calvarium, base of skull and especially the orbital rims are

very dense.

• The facial hones are small and the maxilla hypoplastic.

• The mandible has no angle, that is it is obtuse

• The skull shows failure

of sutural fusion and

sclerosis of the base.

The angle of the

mandible is obtuse

(arrow) and the maxilla

hypoplastic

Thorax, Spine& Hands.• Hypoplasia of the lateral

ends of the clavicles is present to a varying degree.

• The ribs are dense overall.• Failure fusion of the neural

arches and spondylolisthesis are found.

• In adults the vertebral bodies resemble spools, with large anterior and posterior defects.

• Acro-osteolysis occurs, often with irregular distal fragment of distal phalanges

Osteogenesis imperfecta• It is mainly autosomal dominant inheritable disorder of

connective tissue.

• It occurs in about 1/20,000 births and is caused by defects in

the synthesis of collagen I.

• The most serious involvement is in the skeleton, but changes

in ligaments, skin, sclera, the inner ear, and dentition are also

noted.

• There are four major clinical criteria for diagnosis:

osteoporosis with abnormal fragility of the skeleton, blue

sclerae, abnormal dentition and premature otosclerosis.

• Only two of these need be present to confirm the diagnosis.

Classification:TYPE I:

• Over 70%: of cases of ostcogenesis imperfecta fit into this category. It has autosontal dominant inheritance.

• Sclerae are blue. • Bone fragility is mild. • Stature is only mildly reduced. Deafness occurs in adult life.• This group is further divided into :Type IA- normal teeth, minor skeletal change.Type 1B- dentinogenesis imperfecta more severe skeletal

change.• Osteoporosis occurs with cortical thinning with bowed, thin

gracile long bones . • Wormian bones are seen in the skull.

TYPE II:• 10% of cases are due to this spontaneous dominant new

mutation which is usually lethal in utero or early infancy. • The sclerae are dark blue.• Overall the bones are grossly demineralised with thin cortices. • Numerous healed or healing rib fractures are seen at birth. • This group is further divided into:Type 2A- The long bones are bowed, short and broad.

Numerous fractures are seen. The ribs are broad with continuous beading .

Type 2B- The long hones are as in Type 2A, but the ribs show less or no beading.

Type 2C- The long bones are thinned, show numerous fractures and the ribs too are thin and beaded.

• Mineralisation in the skull may be severely retarded. Only the petrous bones may be clearly seen.

• The skull is enlarged and numerous wormian bones are seen.

TYPE III

• This occurs in 15% of patients, is a severe and progressively

deforming type and is usually due to a new mutation.

• Sclerae may he blue at birth but are usually normal in

adolescence.

• Overall the bones are demineralised.

• Vertebral compression is seen and results in kyphoscoliosis.

• The long bones are thin, osteoporotic and shows bowing.

• In the skull, ossification is again poor, sutures are wide and

wormian bones persist.

• This type has associated with abnormal dentation.

TYPE IV

• This group constitutes 5% of patients. There are two subtypes-

Type 4A- no dental lesions

Type 4B- dentinogenesis imperfecta.

• Sclerae are usually normal.

• Fractures are seen at birth.

• Marked osteopenia with mild bony fragility.

• Blue sclera.

• Severe osteoporosis with extreme thinness of the cortices.

• The long bones are thing with marked osteopenia.

• Upper and Lower Extremity is seen. Here multiple fractures have contributed to bowing deformities.

• Multiple fractures contribute to the thick appearance of the femurs and ribs

The femur and pelvic bones are expanded and bowed at the site of previous fractures. They appear cystic, or soap-bubble like appearance.(Intraosseous hemorrhage is believed to be the mechanism leading to the cystic appearance of bone in osteogenesis imperfecta.)

•

• There is severe osteoporosis of the spine and the biconcave appearance of the vertebral bodies.

• Patients with a benign form of the disease may not present until adult life.

• Multiple fractures occur over a few years; eventually the diagnosis is made.

• Healing may be with excessive callus.• Sarcomatous degeneration is rare. • Deafness is found in adults and may be due to ankylosis of

ossicles and osteosclerosis. • The ribs are so soft and thin that the downward pull of the

intercostal muscles makes their posterior portion convex downward.

Differentials:

• Battered baby syndrome: In osteogenesis

imperfecta the fractures are often diaphyseal

rather than metaphyseal, and the urinary

hydroxyproline is often elevated. Mostly seen in

female babies.

• Idiopathic juvenile osteoporosis: This condition

starts just before puberty and is usually self-

limiting. Vertebral compression and

characteristically metaphyseal fractures,

especially of the lower limb long bones are seen.

Osteopetrosis

• Synonyms are: Albers-Schönberg disease, osteosclerosis,

osteopetrosis generalisata, osteosclerosis generalisata, marble

bones, and chalk bones.

• It is a rare hereditary and familial bone abnormality

characterized by the lack of resorption of normal primitive

osteochondrous tissue. The persistence of this tissue inhibits

the formation of normal mature adult bone with a medullary

canal containing marrow tissue.

• The osteoclasts may be unresponsive to parathyroid hormone

and unable to resorb bone and cartilage.

• The primitive calcified cartilage persists in abundance, and a

medullary space is never allowed to form. This leads to

anemia and extramedullary hematopoiesis, causing

hepatosplenomegaly

• There appear to be at least four forms:

(a) a benign heterogenous form, which is autosomal dominant. It is

further sub divided: (Type I) Marked thickening of the sclerotic skull

vault but with an almost normal spine. (Type II) A sclerotic skull

base and a `rugger jersey' spine. Patients with Type II have a high

risk of fracture; those with Type I do not.

(b) a severe malignant form, which is autosomal recessive. It

manifests in infancy or childhood. This has been diagnosed in

utero. Often fatal.

(c) an intermediate recessive type

(d) a recessive type with tubular acidosis (carbonic anhydrase II

deficiency).

Radiological features

• Increased density and thickening of long bones, especially

metaphyses.

• The presence of a `bone within a bone' differentiates osteopetrosis

from the other sclerosing dysplasias. This is due to the cyclic nature

of the disease, so that the dense shadow of formation of abnormal

bone is seen within the outline of the current normal or abnormal

shadow.

• This bone within a bone' may be vertical in the long bone shafts and

digits, transverse at the metaphyses or arcuate beneath the iliac

crests.

• Osteopetrosis-fine vertical lucencies are seen extending to the metaphyses, together with a 'bone within a bone' appearance at the tibial and fibular diaphyses.

• Also note the increased density of bones.

• In long bones the `Erlenmever flask'

deformity due to failure of metaphyseal

remodelling, giving gross distal

undertubulation, and the presence of dense

bone, vertical line lucencies extending to the

metaphyses are also present probably due to

vascular channels being better seen against

dense hone.

• Fractures are usually transverse and heal with

normal callus.

• In Skull- The bones of the skull base are initially affected with sclerosis and thickening, prominent in the floor of the anterior cranial fossa. The sphenoid and frontal sinuses and mastoids are underpneumatised or not at all.

• Neural foramina are encroached upon and blindness results in serious cases.

• In Spine- spondylolisthesis is seen. In vertebral bodies, an appearance like a `rugger jersey' spine may be seen due to the inserted shadow of an earlier, more dense body, especially in benign osteopetrosis sub type II.

Here we see the sclerosis at the skull base. Osteopetrosis predisposes a patient to the development of dental caries and abscess formation. Extensive involvement may lead to osteomyelitis of the mandible as a rare complication (A hemimandibulectomy has been performed as a result of osteomyelitis of the mandible)Underpneumatization of skull bones can also be seen.

• Here we see dense bands along the superior and inferior endplates known as ‘Rugger Jersey spine’

Melorheostosis• It is very rare disease affecting both sexes.

• Patients may complain of pain and of restricted movements of

joints but the condition is often asymptomatic.

• The condition is characterised by the presence of dense

irregular bone running down the cortex of a long bone. Both

the internal and external aspects of the cortex may be

affected. Dense areas tend to be overgrown and bowing may

result. The new bone has been likened to molten wax running

down the side of a burning candle.

• The lesions tend to be segmental and unilateral, though both

limbs may be affected. Occasionally the condition is bilateral

but never symmetrical.

• The lower limbs are most commonly affected.

• Premature epiphyseal fusion may result, so that an affected

limb may be larger or smaller than normal.

• The skull, spine and ribs are rarely affected.

• Ectopic bone may be found.

• The plain film shows eccentric and irregular sclerosis along the medial aspect of the distal femur, crossing the joint into the adjacent tibia. There is new bone on the outer aspect of the cortex and also in the soft tissues

• On the radioisotope bone scan increase in uptake is demonstrated in the areas of bone sclerosis.

• The coronal T,-weighted MR sequence shows sclerotic bone, as expected, as areas of low signal lying within the marrow, on the periosteum and in the soft tissues.

Osteopoikylosis

• This is usually an incidental radiological finding .

• The lesions are familial. It affects both sexes equally and is

characterised by the presence of multiple, dense, radiopaque

spots which are round, oval or lanceolate, and tend to he

situated parallel to the axis of the affected bone.

• They are usually uniform in density but may have relatively

clear central zones.

• Any bone may be affected. They occur especially frequently in

the ends of long hones and around joints, in the carpus and

tarsus, and in the pelvis.

• This lesion must be differentiated from serious conditions such

as tuberous sclerosis and metastases, but their distributions

around joints, and the fact that the nodules rarely increase in

size or number under observation, distinguish this benign

condition from metastases

• The small circular densities that are found surrounding the acetabula and proximal femora are seen here.

• Similar lesions are seen in feet and hand.

Osteopathia striata

• In this asymptomatic disorder sclerotic striations are found in

the long bones, especially of the lower limbs, affecting both

bone ends and diaphysis.

• A fan-like pattern radiating from the acetabulum to the iliac

crest is characteristic of involvement in the ilium and has been

referred to as the sunburst effect.

• Cause is still unknown.

Note the dense bone formation radiating in a fan-like pattern from the acetabulum toward the iliac crest (sunburst effect).

Chondrodystrophia calcificans congenita• This disease exists in at least three types, inherited differently:

• 1. Rhizomelic type (recessive) usually lethal; the most common

fatal type.

• 2. Non-rhizoinelic types (Conradi-Hiinermann) (a.) Dominant-

common, usually mild; (b.) X-linked dominant lethal in males.

• These have similar radiographic changes. Ichthyosis may he

seen in the rhizomelic and X-linked forms.

• The less severe Conradi form of the condition is characterised in

infancy by stippling or punctate calcification of the tarsus and

corpus, long bone epiphyses, vertebral transverse processes and the

pubic bones. The resulting epiphyses in later life are often

misshapen, and deformities with asymmetrical limb shortening

result. The spine often ends up scoliotic.

• The more severe forms usually result in death in the first year;

survivors are likely to be mentally defective. Stippling is present.

Long bones show gross symmetrical shortening and metaphyseal

irregularity. In this form the vertebral bodies show a vertical

radiolucency on the lateral view which does not occur in the

dominant type.

There is irregularity of vertebral bodies and of the neural arches and spinous processes in association with soft-tissue stippled calcification. These changes are also seen at the joints. The long bones are markedly shortened. The humeral metaphyses are irregular.

Multiple epiphyseal dysplasia• This condition is transmitted as an autosomal dominant,

primarily affects the epiphyses. Dwarfism of the short-limb

type may be seen.

• The condition is subdivided into a severe form (Fairbank)

characterised by small epiphyses, and a mild type (Ribbing)

characterised by flat epiphyses.

• In order of frequency, the epiphyses affected are those of the hips, shoulders, ankles, knees, wrists and elbows.

• Epiphyses tend to appear late and are fragmented and flattened; the deformities persist throughout life and cause premature osteoarthritis.

• The femoral capital epiphyses show symmetrical flattening and fragmentation in the immature skeleton, the symmetry distinguishing this from bilateral Perthes' disease.

• The skull is not affected.

Radiological features• 1. Lower tibial epiphysis-the lateral part of the lower tibial

epiphysis is thinner than the medial part. A tibiotalar slant

results.

• 2. The double-layered patella is characteristic but is found in

few cases.

• 3. The femoral and tibial condyles may be hypoplastic and the

intercondylar notch shallow. Flattening of the femoral and tibial

condyles makes the joint look widened.

• 4. Spinal changes are seldom pronounced and may he absent.

The appearances in the spine, if present, resemble

osteochondritis.

• Characteristic Double-layered Patella is seen here.

• Angular condyles and flat intercondylar notch. This is a characteristic appearance though not always present

• CT scan shows the flattening of the femoral heads

Metaphyseal chondrodysplasia

Schmid described a mild type that is relatively common.

Metaphyses of long bones are cupped and resemble rickets.

No biochemical changes are found. The patient may be

wrongly diagnosed as suffering from vitamin D-resistant

rickets.

Mild changes only in upper

femoral metaphyses are noted.

Jansen's metaphyseal chondrodysplasia: Grossly irregular

mineralisation is seen in the metaphyses of tubular bones. A

large gap is also seen between the epiphyses and the

disordered metaphyses.

Extensive changes in all

the pelvic bones are seen.

Other types named after Pena and Vaandrager show

intermediate involvement of metaphyses, less than in the

Jansen type but more than in the Schmid type.

Some cases of metaphyseal chondrodysplasia are associated

with pancreatic insufficiency and neutropenia.

Sometimes metaphyseal changes are associated with lesions

of the spine-such conditions should be designated

spondylometaphyseal dysostosis.

Diaphyseal aclasis

• It is familial and inherited.

• Long bones are mostly affected especially in metaphyseal

region.

• It expands irregularly and is of club shaped.

• These local enlargments are projected osseous excrescences

exostoses, which are round and pointed.

• Their cortex merges with that of the shaft and their cancellous

bone merges with the cancellous bone of the shaft, i.e they

don’t lie upon the cortex.

• Exostoses are also found mainly seen in regions of shoulder,

hips, knees and ankles. Also on vertebral bodies and on medial

border of the scapula.

• The epiphyses are not involved.

• Exostoses may be seen as mall metaphyseal projections in

infants and their growth may be observed.

• During skeletal growth, the bony exostoses are covered by

cartilage cap which undergoes spotty calcification and with

increasing maturity the cartilaginous mass becomes

increasingly dense and smooth margin can be seen.

• Increase in transverse width is often accompanied by shortening so that deformities result. These changes are especially common at the radius and ulna, resulting in Medlung’s deformity.

• Metacarpal bowing, radioulnar syntosis and radial head dislocation may be found.

• Lesions may cause nerve compression and result in neurological deficits.

• Rapid growth may raise possibility of malignant degeneration. The incidence of chondrosarcoma is about 10% and are often around hip.

Common sites of exostosis.

Red- more common sites.Pink- less common sites.

(A.) AP Shoulder. Note the several sessile exostosis involving the cortical margins of the proximal metaphysis of the humerus. (B and C). Bilateral Hands. Observe multiple small projections(arrows) throughout the metacarpals, phalanges, distal radius, and ulna bilaterally.

BAYONET HAND DEFORMITY. Bilateral Forearm x ray show small exostosis, affecting the radius and ulna bilaterally. The bayonet hand deformity is found in approximately 30% of patients with hereditary multiple exostosis affecting the wrist. This deformity occurs as a result of retardation of bone growth and is characterized by shortening of the ulna, outward bowing of the radius, and subluxation of the radioulnar joint.

Thanatophoric dwarfism

• It has been separated from achondroplasia and is the

commonest fatal neonatal dysplasia.

• Radiological findings:

Limbs: There is rhizomelic dwarfism but the long bones are

bowed. The metaphyses are irregular. Epiphyses of the knee

are absent at birth. Short, wide metacarpals and phalanges are

seen.

Axial skeleton: There is marked platyspondyly but the

posterior vertebral elements are normal so that, on an

anterior view, the vertebral bodies resemble the letter H.

• The pelvis shows poor mineralisation of the ischium and

pubis, and small square iliac blades. The skull often

shows lateral temporal bulging ('cloverleaf skull') due to

craniostenosis.

• The ribs are short and flared anteriorly.

• The infants are stillborn or die shortly after birth.

-A clover leaf skull is seen.

-The scapulae are hypoplastic and the

clavicles high.

-Platyspondyly is seen, resulting in H-

shaped vertebral bodies.

-The bones are short and bowed

Xray of 1 day old child shows dysplastic bones with bowing and platyspondyly of vertebrae.

Here we again see dysplastic bones, cloverleaf skull and small and flared ribs.

Other Xrays of same 1 day old baby.

Asphyxiating thoracic dystrophy• Inheritance is autosomal recessive. • Most of the patients with this disease die in infancy from

respiratory distress. • In contradistinction to Thanatophoric dwarfism, the spine is

normal and the long bones are not curved and only a little shortened.

• The thorax is stenotic. • The ribs are short and horizontal and the clavicles highly

placed. • In those patients who survive, renal failure may result.

Short horizontal ribs with

high clavicles but a normal

spine. The scapulae are

hypoplastic.

Chondroectodermal dysplasia• 50% patients have congenital cardiac defects which may be

fatal. The inheritance is autosomal recessive.

• Radiographic features:

Limbs: the paired long bones are short and the metaphyses

dome-shaped; the dwarfism is mesomelic. At the proximal

tibia the developing epiphysis is situated over the abnormal

medial tibial plateau and is defective laterally, so that valgus

deformity results. Polysyndactyly is also present.

• Axial skeleton: The skull and spine are normal. The rib are

short and horizontal. The acetabulum has a medial spur in the

region of the tri-radiate cartilage. The ectodermal dysplasia,

with partial or total absence of teeth, and abnormal hair and

nails, are not seen in asphyxiating thoracic dystrophy.

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