CONNECTIVE TISSUE DISORDERSPresenter: Dr. Gituri Philip

Moderator: Dr. Kingori

Outline

1. Introduction

2. Classification & Types of connective tissue diseases

3. Presentations of CTDs

4. Specific Issues

5. Conclusions

Introduction to CTDs

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

Collagen

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

Cont…

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

i. Schmid’s metaphyseal chondrodysplasia (affects the hypertrophic physeal zone).

Cont…

Collagen type XIan adhesive that holds the collagen lattice together

Introduction

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

the type of mutation

the role & function of the affected protein on musculoskeletal structure

Types of collagen

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

Marfan syndrome

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

Diagnosis

Clinical assessment mutational or linkage analysis in familial phenotypes

Classification of Marfans syndrome

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

Treatment

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

Ehlers-Danlos syndrome (EDS)

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

Clinical Presentation

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 (3rd or 4th decade)

Muscle hypotonia & delayed gross motor development

Importance to surgery

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

Beighton Criteria for Joint Hypermobility

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

Treatment

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

Osteogenesis imperfecta (OI)

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

Clinical presentation of OI

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

Type Severity Features Sclerae Inheritance

IA, IB Mild Most common, mild to moderate bone fragility, little or no deformity

Blue AD

II Lethal, rarely survive infancy

Extremely fragile bones, severe deformity, perinatal

Blue AR

III Severe Progressively deforming, moderate to severe deformity, progressive, neonatal fractures

Normal AR

IVA, IVB Moderately severe

Mild to moderate bone fragility, long bone/spine deformity, A with dental involvement

Normal AD

Treatment of OI

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

Other collagen associated diseases

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.

Scurvy

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)

features of scurvy on X-ray of long bones

Scurvy cont…

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.

Multiple epiphyseal dysplasia

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

Treatment of MED

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.

Spondyloepiphyseal dysplasia

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.

Kniest Syndrome 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.

Arthritides

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 cartilagemultiple hot, swollen, morning stiffness. Subcutaneous calcified nodules and iridis Radiographs: symmetric joint space narrowing, periarticular erosions, and osteopenia

Treatment of RA

1.Nonsurgical: NSAIDs & DMARDs

2.Surgical

i. synovectomy

ii. joint realignment early

iii.joint arthroplasty later stages.

Conclusions

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