Conditions with Abnormal Collagen, orthopedics

1. Conditions with abnormal
collagen
Dr V Singh Chauhan
Orthopedic Resident
Moderator : Prof Gakuu/ Dr GakuyaDr. Virinderpal Singh Chauhan

2. Scope
• Collagen types and associated abnormalities
• Selected conditions
– Type 1
• Osteogenesis Imperfecta
• Ehlers Danlos
– Type 2
• Kniest Dysplasia
• Spondyloepiphyseal Dysplasia (SED)
– Type 9
• MED
– Others
• Scurvy
Dr. Virinderpal Singh Chauhan

3. Collagen
• Primary structural protein of body
– Occurs in bone, cartilage and tendons
• 29 types identified each with triple helix of
alpha chains
• Differences in each due to amino acid
sequence
• Collagenopathies usually affect many organ
systems
Dr. Virinderpal Singh Chauhan

4. Types of collagen
Types of Tissues
 I Skin, tendon, bone, meniscus, annulus fibrosus
 II Articular cartilage, vitreous humor, nucleus pulposus
 III Skin, muscle, blood vessels
 IV Basement membrane (basal lamina)
 V,VI,IX,X Articular cartilage
 X Articular cartilage, mineralization of cartilage in
hypertrophic zone of physis
 XI Articular cartilage
 XII Tendon
 XIII Endothelial cells
Dr. Virinderpal Singh Chauhan

5. Collagenopathies
• Inherited genetic defects of collagen
synthesis
• Can be minor or major (disability)
• Severity depends on type of mutation &
role + fxn of affected protein
Dr. Virinderpal Singh Chauhan

6. Collagenopathies
• Type 1
• Ostegenesis Imperfecta
• Ehlers Danlos type 1,2,7
• Type 2
• Kniest Dysplasia
• Spondyloepimetaphyseal dysplasia
• Type 3
• Ehlers Danlos type 3 & 4 (Sack Barabes Syndrome)
• Type 9
• Multiple Epiphyseal Dysplasia
• Type 10
• Schmid’s Metaphyseal Chondrodysplasia
• Type 11
• Sticklers Syndrome
• Marshall Syndrome
• Multiple
• Scurvy
Dr. Virinderpal Singh Chauhan

7. Type 1 Collagenopathies
Osteogenesis Imperfecta Ehlers Danlos Syndrome
Dr. Virinderpal Singh Chauhan

8. Osteogenesis Imperfecta
• A.k.a Fragilitus Ossium / Brittle Bone Dx
• Pathogenesis
– Impaired mutation Type 1 collagen
– Mutation – COL1A1 & COL1A2 genes
– Impaired cross links preventing production of
polymerized collagen
– Fracture Healing not impaired with large amounts of
callus formation
Dr. Virinderpal Singh Chauhan

9. Clinical Manifestations
• Bone fragility and fractures
fractures heal in normal fashion initially
but the bone is does not remodel
can lead to progressive bowing
• Ligamentous laxity
• Short stature
• Scoliosis
• Codfish vertebrae (compressionfx)
• Olecranon apophyseal avulsion fx
Dr. Virinderpal Singh Chauhan

10. Non-Orthopaedic manifestations
• Blue sclera
• Hearing loss
lessfrequentthangenerallysuspected
• Dentinogenesis imperfecta
brownish opalescent teeth
• Wormian skull bones
(puzzlepieceintrasuturalskullbones)
Dr. Virinderpal Singh Chauhan

11. Clinical Diagnosis
• Symptoms
– Mild Cases – multiple #s during childhood
– Severe - #s at birth. Maybe fatal
• Signs
– Sabre Shin Appearance
– Bowing of bones
– Scoliosis
Dr. Virinderpal Singh Chauhan

12. Classification of OI - Sillence
• Type 1
– Mildest
– Presents at Pre-school age
– Autosomal Dorminant
– Blue Sclera
– Hearing deficit in 50%
– Avulsion #s common due to decreased tensile
strength of bone
• Type 2
– Autosomal Recessive
– Lethal in perinatal period
– Blue Sclera
Dr. Virinderpal Singh Chauhan

13. Classification of OI - Sillence
• Type 3
– Autosomal recessive
– Normal Sclera
– #s at birth
– Progressive short stature
– MOST Severe survivable form
– Xtic triangular face due to large skull and underdeveloped facial
bones
• Type 4
– Moderately severe
– Autosomal Dorminant
– Bowing of bones + Vertebrae #s common
– Normal Hearing
– White Sclera
Type 5,6,7 added to original
classification.
No real mutation but Abnormal
bone on microscopy
5 – Hypertorphic Callus after #
Dr. Virinderpal Singh Chauhan

14. Dr. Virinderpal Singh Chauhan

15. Management
• Fracture
– Prevention
• Early Bracing
• Bisphosphonates
– Suppress activity of osteoclasts hence px bone mass loss &
resorption
– Role of cyclic IV Palmidronate….drug holiday/efficacy??
– Issues
» Jaw necrosis
» Atypical Subtroch & femoral stress #s
» Radiographic Changes consistent with Osteopetrosis
Decrease Deformities
Stabilize Lax Joints
Decrease # Incidence
Dr. Virinderpal Singh Chauhan

16. Management
• Fracture Treatment
– Non op if < 2ys
– Op
• Pt > 2ys
– Telescopic rods
• Sofield Miller Procedures
– Correctional for Severe deformities
– “Sausage” procedure
– Scoliosis
• Observe if <45 degrees
• Bracing ineffective
• Operative – posterior fusion
Dr. Virinderpal Singh Chauhan

17. Ehler Danlos Syndrome
• Collection of multiple subtypes involving
different collagen types
• Common phenotypic xtic
– Hyperextensibility of skin
– Hypermobility of Joints
– Easy bruising
• 40-50% have COL5A1 or COL5A2 mutations
associated with type 5 collagen
Dr. Virinderpal Singh Chauhan

18. Associated Features
• Soft tissue calcifications
• Mitral Valve prolapse
• Aortic root dilatation
• DDH
• Club foot
• Pes planus
• High Palate
• Gastroparesis
Dr. Virinderpal Singh Chauhan

19. Classification
• Berlin Classification
– Old
– Types 1 – 11
• Villefranche Classification – 1998
– 6 subtypes
• Classical
• Vascular
• Hypermobility
• Kyphoscoliosis
• Arthrochalasis
• Dematosparaxis
Dr. Virinderpal Singh Chauhan

20. Dr. Virinderpal Singh Chauhan

21. Orthopedics Manifestations
• Subluxations & Rec. Dislocations of Joints
– Habitual Shoulder/patella dislocations
– Mx
• Conservative
– Ban voluntary dislocations (attention seeking)
– Intensive muscle training exercises and avoid high contact
activities
Avoid surgical procedures unless absolutely necessary
Risk of reccurence HIGH esp for soft tissue operations since all
tightened tissues will start to stretch again
Ligaments usually tighten up with age of pt hereDr. Virinderpal Singh Chauhan

22. Ortho Manifestations
• Surgery
– Procedures involving bone sx such as
osteotomies have higher success rate than
those targetting ligaments/tendons
• E.g. Osteotomies to change direction/location of
insertion of tendons
• Osteotomies to provide a large joint area
– Tibial tubercle transfer for patellar dislocation
– Femoral + pelvic osteotomies for hip subluxation
Dr. Virinderpal Singh Chauhan

23. Ortho Manifestations
• Scoliosis
– Develop at early stage & progressive
– Common – 50%
– Mx as per similar principles as idiopathic scoliosis
• Pseudotumors
– At susceptible sites e.g. elbows/knees
– Due to easy bleeding
• Dehiscence & Gaping of wounds with abnormal scar
formation
Dr. Virinderpal Singh Chauhan

24. Type 2 Collagenopathies
• Kniest Dysplasia
• Spondyloepiphyseal Dysplasia
Dr. Virinderpal Singh Chauhan

25. Kniest Dysplasia
• Rare
• Autosomal dorminant
• Defect – COL1A1
• Abnormality – Type 2 collagen
• Presentation
– Disproportionate Short trunk dwarfism
– Enlarged Joints and stiffness
– Scoliosis / Kyphosis
– Cleft lip
– Flat face
– Prominent eyes due to shallow sockets
– Bell Shaped chest
Dr. Virinderpal Singh Chauhan

26. Kniest Dysplasia
• Orthopedic Manifestations
– Short stature
– Club foot
– Disprop short trunk dwarfism
– Early OA
– Joint stiffness / contractures
– Scoliosis / Kyphosis
– Hypoplastic pelvis
• Medical manifestations
– Respiratory complications - Cleft Palate
– Otitis Media with hearing loss - Retinal Detachment
Dr. Virinderpal Singh Chauhan

27. Kniest Dysplasia
• Imaging
– Osteopenia
– Dumbell shaped metaphyseal bone
– Coxa vara
– Genu valgum
– Swiss cheese appearance of bone cartilage
• Small holes in bone cartilage
• Rx
– Early therapy for joint contractures
– Reconstructive procedures for early hip degenerative
arthritis
Dr. Virinderpal Singh Chauhan

28. Spondyloepiphyseal Dysplasia
• Mutation – COL2A1
• 2 types
– SED Congenita – Autosomal dorminant – severe
– SED Tarda – X-linked, Milder form
• Usually affects vertebrae and epiphysis
Dr. Virinderpal Singh Chauhan

29. Orthopedic Manifestations
• Short stature
• Short neck, widespread eyes
• Barrel Shaped chest
• Angular deformities esp Genu Valgum
• Lumbar lordosis
– Due to hip flexion contractures
– Give abdomen a protrusional app
• Waddling gait – coxa vara
• Club foot
• Associated conditions
– Cleft Palate - Cataracts
– Retinal detachment - Deafness
– Nephrotic syndrome - Tarda
Dr. Virinderpal Singh Chauhan

30. Xrays
• Delayed appearance of epiphysis
– Femoral heads not seen until pt = 5ys
• Normal – 4-6/12
– When seen – flattened & irregular epiphysis
• Coxa Vara
• Platyspondyly
• Kyphoscoliosis
• Odontoid hypoplasia / os odontoideum
– Check for atlanto-axial instability
Delay in ossification of femoral heads + coxa vara
Platyspondyly (flattened vertebrae)
Severe degenerative arthritis 15yr old with dislocated hipsDr. Virinderpal Singh Chauhan

31. SED
• Rx
– Atlantoaxial instability a concern
• Early occipitocervical spondylodesis
– Coxa Vara
• Valgus corrective osteotomy if angle <100 or is
progressive
– Scoliosis
• Manage operatively if angle>40
Dr. Virinderpal Singh Chauhan

32. Type 9 Collagenopathy
• Multiple Epiphyseal Dysplasia (MED)
– Dwarfism xtised by delayed + irreg ossification at
multiple epiphysis
– Genetic
• Defect – COMP (Cartilage Oligomeric Matrix Protein) gene
• Mutation – COL9A1/A2/A3
– Ass. With Type 2 collagenopathy since type 9 acts as link points for
type 2
• Autosomal dorminant
• Autosomal recessive – rare (Early OA/Clubfoot/multiple layered
patella/brachydactyly)
Issue – Failure of formation of secondary ossification centre
Femoral + humeral heads commonly affected.Dr. Virinderpal Singh Chauhan

33. • Types
– Fairbank
– Ribbing – milder form
• Clinically
– Short limbed dwarf
– Joint pains – often don’t manifest until 5-14 yrs
– Waddling gait
– Flexion contractures of knee/elbow
– SPINE + PELVIS - NORMAL
Dr. Virinderpal Singh Chauhan

34. Xrays
• Pelvis
– Bilateral epiphyseal defects
• Mimics Perthes
– In MED – its simultaneous + bilateral + acetab changes seen
• Knee
– Valgus knee
– Double Layered Patella
• Due to irreg ossification of patella
– Tibial slant sign
• Hand & Foot
– Short, stunted metacarpals/metatarsals
– Hyperextensible fingers
Irregular ossification + Double
layered patella
Dr. Virinderpal Singh Chauhan

35. Mx of MED
• Ortho rx rarely necessary in children
• Osteotomies to correct angular deformities
esp around knee
• Degenerative Arthritis – symptomatic rx
– ?Early THR
Dr. Virinderpal Singh Chauhan

36. Scurvy
• Vitamin C deficiency. Ascorbic acid synthesis not done in
the body and relies on external sources
• Ascorbic acid needed in redox rxn to hydroxylate proline
and lysine
• Leads to decreased collagen formation and any collagen
formed is of poor quality
• New bone formation is prevented and old bone becomes
brittle
• H’age tendency due to fragility of capillary walls
Dr. Virinderpal Singh Chauhan

37. Scurvy
• Bleeding subperiosteally + Marrow
particularly in metaphysis adj to actively
growing epiphysis
– Interferes with growth of osteoblasts into
calcified bone
• Failure of conversion of calcified cartilage into
bone
Dr. Virinderpal Singh Chauhan

38. Clinically
• Irritable child
• Pseudoparalysis
– Extremeties held immobile due to muscle spasms
• Subperiosteal h’age
– Palpable, soft & extremely tender swelling fixed to bone
• Gums bluish, tender, bleeding
• Petechial h’age
• Epiphyseal separation distal femur, upper tibia & humerus
• Scorbic rosaries due to costochondral separation
Dr. Virinderpal Singh Chauhan

39. Imaging
• White Line of Frankel
– Widened zone of provisional calcification btwin epiphysis & metaphysis
– Due to excessive calcified cartilage acc.
• Trummerfield zone
– Transverse radioluscent band in metaphysis adj to frankel line
– Aka Scurvy Line
– Due to metaphyseal response to h’age undergoing hyperemia = increased resorption
of bone
• Wimberger Line
– Ring of increased density surrounding epiphysis (zone of calcified cartilage in
epiphysis)
• Pelkan Spur & #
– Metaphyseal
– Protrusion from lateral or medial border of epiphysiometaphyseal jxn
Dr. Virinderpal Singh Chauhan

40. Imaging
• Corner Sign of Parker
• Thin cortices
– Pencil point cortex
• Decreased Trabeculae with ground glass
appearance
• Subperiosteal elevations
• #s and dislocations
– Due to weakening of epiphysiometaphyseal jxn
Dr. Virinderpal Singh Chauhan

41. Mx
• Vitamin C supplements & rich food
• Immobilize #s and painful joints with plaster
splints
Dr. Virinderpal Singh Chauhan

42. Dr. Virinderpal Singh Chauhan