dr Bipul Borthakur

1. DEVELOPMENTAL CONDITIONS OF
MUSCULOSKELETAL SYSTEM
• DR BIPUL BORTHAKUR
PROF OF ORTHOPAEDICS,SILCHAR,ASSAM,INDIA

2. Conditions to be discussed :
• Osteogenesis Imperfecta
• Mucopolysaccharidosis IV
• Dysplasia Epiphysealis Multiplex
• Dysplasia Epiphysealis Punctata
• Osteopetrosis
• Ollier Disease
• Hereditary Multiple Exostoses
• Achondroplasia

3. Osteogenesis Imperfecta
• Genetic disorder of connective tissue
• Defect in genes encoding Type I Collagen formation
• Most commonly genes affected are COL1A1 and COL1A2
• Pattern of inheritance can be Autosomal dominant,Autosomal recessive
or sporadic.

4. CLINICAL FEATURES
• Multiple long bone fractures
• Skeletal deformity
• Blue sclera
• Hearing loss
• Fragile opaque teeth(dentinogenesis Imperfecta )

6. X-Ray findings
Marked osteoporosis
Thinned out cortices
Loss of trabeculations

7. LABORATORY DIAGNOSIS
• Normal serum calcium
• Normal serum phosphorus
• Diagnosis can be made with clinical and radiological findings.
• Confirmatory results through genetic analysis.

8. MANAGEMENT
• Cyclic Pamidronate reduces bone pain and fracture rate.
• Surgery indicated to correct deformities.
• Intramedullary rods used.
• External immobilisation is limited.

10. Mucopolysacchaidoses IV
• Also called Morquio-Brailsford disease.
• Autosomal recessive lysosmal storage disorder.
• Two subtypes
• Type A (classical) with defect of N-acetylgalactosamine-6-sulphate.
• Type B (variant) with a defect of beta-galactosidase.

11. Clinical picture : MPS IV A(classical)
• Child appers normal during initial 3-4 years.
• Marked kyphotic deformity
• Failure to gain height
• Normal intelligence
• Progressive weakness of musculature
• Chest is narrowes in transverse diameter and elongated in antero-posterior
diametet(pectus carinatum)
• Recurrent respiratory infection

12. Note typical dwarfism, knock knees and crouched
position in Mucopolysaccharidoses IV
Pain is unusual
Survival beyond childhood is rate.

13. Clinical picture : MPS IV B(Variant)
• Manifestations delayed for several years
• Very mild symptoms
• Pain is severe in this variant
• Intelligence is normal

14. X-Ray findings in MPS IV
• Characteristic findings occur in spine and hip
• Vertebrae are flattened and elongated antero-posteriorly
• Delayed ossification of upper femoral epiphysis
• Acetabulum is large and irregular

15. Treatment: MPS IV
• No specific treatment
• Supportive symptom based treatment
• Regular follow up to monitor disease progression

16. Dysplasia Epiphysealis Multiplex
• Autosomal dominant inheritance
• Abnormal ossification of many epiphysis
• Stunting of growth
• Tendency is towards improvement and the epiphysis being
moderately deformed
• Degenerative arthritic changes in the adult

17. X-Ray findings
• Centres of ossification appears late
• Arranged in mulberry like fashion around
one main nucleus
• Eventually,epiphysis becomes normal in density
• Epiphysis is flattened
• Degenerative changes apperars in adult
Note the narrowing and degenerative changes that
restrict shoulder motion.

18. Dysplasia Epiphysealis Punctata
• Also called chondrodystrophia calcificans congenita and stippled epiphysis
• Throughout entire body,multiple focal areas of calcification develop in
cartilagenous precursors of bones.
• Spots found especially in epiphysis
• Subject usual stillborn

19. X-Ray Findings
• Opaque,discrete or coalescing dots occupy cartilgenous structures
• Metaphyses are splayed
• Epiphyseal borders appear irregular

20. Osteopetrosis
 Also called Albers-Schonberg disease,marble bone disease and chalk bones.
 Developmental condition characterised by increased bone density ,remodelling defect and
pathological fractures.
 Incidence of Autosomal dominant is 1 in 20000 births
 Incidence of Autosomal recessive is 1 in 250000 births
 Caused by failure of osteoclast development or function

21. Clinical picture of Osteopetrosis(recessive variant)
• Autosomal recessive is life-threatening condition
• Manifests in infancy with predisposition to fractures and
osteomyelitis
• Short stature follows impairment of longitudinal growth
• Typival facial appearance results from macrocephaly and frontal
bossing
• Expanding bone can narrow nerve foramina resulting in
blindness, hearing loss and facial palsy
• Children at risk of developing hypocalcemia and tetanic seizures
• Most severe complication is bone marrow suppression resulting
in life-threatening pancytopenia

22. Clinical picture: Osteopetrosis (dominant variety)
• Typically has onset on late childhood
• Complications are confined to skeleton including fractures, scoliosis and
osteomyelitis particularly affecting mandible with dental caries or abscess
• Cranial nerve compression is rare affecting around 5 % of individuals

23. X-Ray findings : Osteopetrosis
• Entire long bone may be dense and completely devoid of structures
• Occasionally, less dense areas of normal bone are interspersed
• Metaphysis are chiefly affected becoming clubbed
• Illia show alternating fense and clear bands parallel with the
crests(bone with ina bone)
• Air sinuses are absent or dense
• Vertebrae displays dense bands at either end and a clear band
between (sandwich vertebrae)

25. Management of osteopetrosis
• Routine dental and ophthalmologic surveillance
• Maintenance of oral hygiene
• Fractures are a difficult orthopaedic intervention because of brittleness of
bone and frequent occurrence of secondary complications such as non-union,
delayed union and osteomyelitis.

26. Ollier Disease
• Also called dyschondroplasia and multiple enchondromas
• Characterised by asymmetrical polyostotic distribution of large
rounded masses of cartilage in metaphysis of bones
• Prevalence is 1:100,000
• Chiefly involved are long bones particularly at more rapidly
growing ends(about knee and distal ends of radius and ulna)

27. Clinical picture: Ollier disease
• Patient usually is affected in first decade of life.
• Affected extremity is shortened
• Skeletal deformities such as gross deformity of hand
• Fractures are uncommon except at hand
• Malignant transformation in 20-50 % of cases

28. X-ray findings : Ollier disease
• Cartilage filled clear spaces of
varying sizes in metaphysis .
• Separate by dense septa of bone
causing a striated appearance.
• Diaphyses is short and thick.

29. Management : Ollier disease
• No medical management .
• Surgery indicated in case of complications such as pathological
fractures,growth defect and malignant transformation.
• A periodic annual surveillance is recommended .

30. Hereditary Multiple Exostoses
• Also called hereditary deforming dyschondroplasia
• Many osteocartilagenous exostoses form at metaphysis of long
bone
• Autosomal dominant condition
• EXT1 and EXT2 gene mutations are responsible
• Prevalence is 1:50,000
• Only bones arising in cartilage are involved.

31. Clinical picture : Exostoses
• Patient may or may not be of short stature depending on the severity
• Irregular hard prominences near ends of long bones visible or palpable
• Commonly affected site are the shoulders,knees and ankles
• Overlying skin if subject to pressure, is tender, reddish and swollen

32. • Paresthesia and muscle weakness resulting from nerve pressure
• Movement restriction due to adjacent tendon involvement
• Malignant transformation may occur resulting in pain and enlargement

33. X-ray findings
• Trumpet like metaphysis
• Poorly trabeculated metaphysis
• Thin cortex

34. Management
• Affected individuals have a 50 % chance of transmitting the disorder, so prenatal
counselling can be offered
• Annual surveillance of the axial sites of osteochondroma is recommended
• Exostoses is removed when complications occur such as infection, tendon
involvement, nerve compression, deformity etc.

35. Achondroplasia
• Also called Chondrodystrophia fetalis
• Characterised by defective enchondral ossification affecting mainly
long bones and disproportionate dwarfism in which the extemities
are shortened and trunk remains relatively unaffected
• Autosomal dominant witn full penetration
• Locus mapped to chromosome 4p16.3
• Incidence is 1 in 20,000 live births
• Point mutation in fibroblast growth factor receptor 3 (FGFR 3) gene

36. Clinical picture : Achondroplasia
• Dwarfism soon after birth
• During growth, extremities lag behind trunk leading to disproportionate
dwarfism
• Hyperextensibility of joints
• Trident appearance of hands
• Well developed musculature

37. • Pelvis tilted forwards
• Hip is posterior to central axis of pelvis
• Rolling gait
• Brachycephalic head
• Chest small and flat
• Normal sexual development

38. Management
• Prenatal ultrasound screening
• Monitoring of growth curves specific for achondroplasia
• Obesity common, so dietary management should begin early and maintained
throughout life
• Shunting for raised intracranial pressure

39. • Decompression for cord compression and canal stenosis
• Osteotomies to correct bowing of legs
• Surgical limb lengthening in carefully selected patients
• Fertility normal but caesarean section required as pelvis is
inadequate

40. अथ चैनं ननत्यजातं ननत्यं वा मन्यसे मृतम् |
तथापि त्वं महाबाहो नैवं शोचचतुमहहसस || 26||
atha chainaṁ nitya-jātaṁ nityaṁ vā manyase mṛitam
tathāpi tvaṁ mahā-bāho naivaṁ śhochitum arhasi
meaning-If, however, you think that the self is subject to
constant birth and death, O mighty-armed Arjun, even
then you should not grieve like this.