Presenter: Dr. Gituri Philip
Moderator: Dr. Kingori

1.
Introduction
2.
Classification & Types of connective tissue diseases
3.
Presentations of CTDs
4.
Specific Issues
5.
Conclusions

 May affect predominantly bone, bone and soft tissues, systemic,
 May complicate orthopedic procedures
 musculoskeletal operations differ in preoperative preparations & outcomes
 May be classified into:
1.
Congenital
2.
Acquired
3.
Inflammatory
4.
Immune-mediated

1.
40% of the dry weight of bone is Organic components
 Collagen (90% of organic component)
 Collagen is primarily type I: provides tensile strength
2.
Type II collagen
 95% of collagen content in articular cartilage
 Provides cartilaginous framework and tensile strength
 Very stable, with a half-life of approximately 25years

 Collagen type X
 Produced by hypertrophic chondrocytes during enchondral ossification: i.
Growth plate ii.
Fracture callus iii.
Heterotopic ossification formation iv.
Calcifying cartilaginous tumors
 Is associated with calcification of cartilage
 A genetic defect in type X collagen responsible for
 Schmid’s metaphyseal chondrodysplasia (affects the hypertrophic physeal zone).

 Collagen type XI
 an adhesive that holds the collagen lattice together

 Inherited disorders of connective tissue: clinically and genetically diverse group of conditions affecting primarily the skin, joints, and, often, the cardiovascular system.
 severity of the musculoskeletal phenotype depends on i.
the type of mutation ii.
the role & function of the affected protein on musculoskeletal structure

Type 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

 Incidence is 1 in 10,000
 Autosomal dominant; 25% new mutations
 Mutation in fibrillin-1 gene on chromosome 15q21; multiple mutations identified
 Affected individuals:
 Dolichostenomelia
 Arachnodactyly
 Positive wrist sign (Walker sign)
 Positive thumb sign (Steinberg sign)

 Arm span-to-height ratio >1.05
 Cardiac defects, especially aortic root dilatation
 Scoliosis is seen in 60% to 70% of patients
 dural ectasia is common (>60%)
 Pectus excavatum and spontaneous pneumothoraces
 Pectus carinatum or asymmetric deformity of anterior chest
 Superior lens dislocation (ectopia lentis) and myopia
 Protrusio acetabuli and severe pes planovalgus

 Clinical assessment
 mutational or linkage analysis in familial phenotypes

1.
Ghent system: 1 major criterion in each of two different organ systems and involvement in a third system
2.
MASS (mitral valve prolapse, aortic root diameter at upper limits of normal, stretch marks, skeletal manifestations of Marfan) phenotype

i.
Multi-disciplinary ii.
Nonsurgical a) Beta blockers for mitral valve prolapse, aortic dilatation b) ii. Bracing for early scoliosis, pes planovalgus iii.
Surgical a) For progressive scoliosis- long scoliosis fusion b) progressive protrusio acetabuli, closure of the triradiate cartilage c) progressive pes planovalgus, corrective surgery

 hypermobile joints, hyperextensible skin, fragile tissues extremely susceptible to trauma
 40% to 50% of patients: mutation in COL5A1 or COL5A2 (type V collagen gene)
 7 types
 classic form: AD
 Type VI, AR (mutation in lysyl hydroxylase. Severe kyphoscoliosis characteristic)
 Type IV, AD(mutation in COL3A1 thus abnormal collagen III; arterial, intestinal, and uterine rupture seen

 Skin: velvety and fragile. Severe scarring with minor trauma common
 Joints: hypermobile, esp the shoulders, patellae, and ankles
 Pes planus
 “double-jointed” fingers
 frequent sprains or subluxation of larger joints spontaneously or after slight trauma
 1/3 of patients: aortic root dilatation
 vascular subtype: spontaneous visceral or arterial ruptures

 c/o chronic joint and limb pain despite normal skeletal radiographs
 joint hypermobility leads to the onset of OA (3 rd or 4th decade)
 Muscle hypotonia & delayed gross motor development

 skin splits from trauma,
 is relatively painless
 does not bleed excessively,
 wounds tend to gape
 wound margins tend to retract
 heal slowly& often become infected
 Dehiscence common, &
 complete wound breakdown may require repeated suturing or healing by secondary intention

1.
Passive dorsiflexion of the fifth finger > 90 degrees
2.
Passive apposition of the thumbs to the flexor aspect of the forearm
(Beighton sign)
3.
Hyperextension of the elbow > 10 degrees
4.
Hyperextension of the knees > 10 degrees
5.
Ability of the palms to completely touch the floor during forward flexion of the trunk with knees fully extended

1.
triad of a) anticipatory guidance, b) pain management c) Physical therapy
2.
Avoid surgery for lax joints; soft-tissue procedures unlikely to work
3.
Progressive scoliosis in type VI (necessary )
4.
Orthopedic procedures: Bracing & longer fusions for
Progressive scoliosis in type VI

 Types I through IV : mutation in the COL1A1 and COL1A2 genes
 bone that has decreased number of trabeculae and cortical thickness (wormian bone)
 Types V through VII no collagen I mutation but o similar phenotype and o abnormal bone on microscopy

 Child abuse should not be ruled out
 types II and III, basilar invagination and severe scoliosis may occur
 Olecranon apophyseal avulsion fractures characteristic
 dentinogenesis imperfecta, hearing loss, blue sclerae, joint hyperlaxity, and wormian skull bones
 frequency of fractures declines sharply after adolescence

II
III
Type
IA, IB
IVA, IVB
Severity Features Sclerae
Mild Most common, mild to moderate bone fragility, little or no deformity
Blue
Lethal, rarely survive infancy
Extremely fragile bones, severe deformity, perinatal
Severe
Blue
Progressively deforming, moderate to severe deformity, progressive, neonatal fractures
Normal
Moderately severe Mild to moderate bone fragility, long bone/spine deformity, A with dental involvement
Normal
AR
AR
Inheritance
AD
AD

 multi-disciplinary approach.
 Manage fractures with light splints
 IV & PO Bisphosphonates and growth hormone
 severe bowing of the limbs or recurrent fracture: intramedullary fixation is indicated with or without osteotomy.
 Progressive scoliosis/basilar invagination is treated with spinal fusion
 Transplantation of adult mesenchymal stem cells

1.
Scurvy
 Acquired: vitamin C deficiency
 decrease in chondroitin sulfate and collagen synthesis
 greatest deficiency seen in the metaphysis
 P/E: microfractures, hemorrhages, and collapse of the metaphysis
 Characteristic radiographic findings :line of Frankel and osteopenia of the metaphysis.

 Vitamin C (ascorbic acid) deficiency
 Produces a decrease in chondroitin sulfate synthesis
 defective collagen growth and repair
 impaired intracellular hydroxylation of collagen peptides
 Clinical features: i.
Fatigue ii.
Gum bleeding iii.
Ecchymosis iv.
Joint effusions v.
Iron deficiency
 Radiographic findings: o thin cortices & trabeculae and metaphyseal clefts
(corner sign)

o normal bone formation reduced o lacking in tensile strength o defective in structural arrangement o Bow legs o stunted bone growth o swollen joints.

 gene mutation is in COMP
 AD
 Radiologic findings: irregular, delayed ossification at multiple epiphyses
 P/E: Short, stunted metacarpals and metatarsals,
 irregular proximal femora,
 abnormal ossification (tibial “slant sign” & flattened femoral condyles, patella with double layer)
 valgus knees (early osteotomy should be considered),
 waddling gait, and early hip arthritis

 14yr old

1.
bone survey to differentiate between MED and single epiphyseal dysplasia, as well as to identify all areas of involvement.
2.
Treat limb alignment and perform early joint replacement.

 Genetic defect: gene encoding type II collagen
 abnormal epiphyseal development in the upper and lower extremities
 Scoliosis: sharply curved apex over a small number of vertebrae
 Retinal detachment and respiratory problems common
.

 Defect within type II collagen
 AD inheritance
 Presentation
• short-trunked, disproportionate dwarfism
• joint stiffness/contractures,
• Scoliosis, kyphosis,
• dumbbell-shaped femora, and hypoplastic pelvis and spine
• Otitis media and hearing loss frequent
 Xray: Osteopenia and dumbbell-shaped bones
 Rx: Early therapy for joint contractures.
 Reconstructive procedures for early hip degenerative arthritis.

Rheumatoid (seropositive) arthritis (RA)
 inflammatory autoimmune arthritis
 causes joint destruction at a younger age
 synovium thickens, fills with B-cells, T-cells, and macrophages, that erode the cartilage
 multiple hot, swollen, morning stiffness. Subcutaneous calcified nodules and iridis
 Radiographs: symmetric joint space narrowing, periarticular erosions, and osteopenia

1.
2.
i.
ii.
iii.

1.
Mutation in the genes coding for various collagen a chains result in a heterogeneous group of heritable conditions (collagenopathies)
2.
Mutations in types II, IX, and XI collagens affects the musculoskeletal, ocular, visual systems, or all three
3.
Diagnosis : clinical findings, radiographic findings, & genetic test results
4.
Follow-up and management: multidisciplinary
5.
Rx is symptomatic and individualized