Connective Tissue Pathology

Question 1

Osteogenesis imperfecta definition and genes affected

Answer 1

Deficiencies in synthesis of type 1 collagen

most common inherited disorder

Genes affected are COL1A1 and COL1A2
- causes substitution in glycine residues which disrupts the triple helical structure of collagen making it not work.

Question 2

Osteogenesis imperfecta clinical signs

Answer 2

Blue sclera: caused by visualization of the underlying choroid in the eye

Hearing loss: related to abnormal development of the bones of the ear.

Dental imperfections: related to deficiency in dentin and collagen.

Question 3

The severity of osteogenesis imperfecta is based on what?

Answer 3

How disrupted the helix structure of collagen is

• unable to form helix at all = death

Question 4

Marfan syndrome characteristics

Answer 4

Disorder of connective tissue by changes in skeleton, eyes and cardiovascular system.

Gene FBN1 Is mutated causing fibrillin-1 deficiency.

Causes elastic fibers to lose elasticity due to improper microfibril formations

usually transmitted familial and in autosomal dominant inheritance pattern

can be de novo mutations

Question 5

Does the size of genes affect likelihood of mutations?

Answer 5

Yes, larger = more likely

Question 6

Most likely areas affected by Marfan syndrome

Answer 6

Aorta, ligaments and ciliary zonules in lens of the eye

Question 7

What cytokine is produced in excess during Marian syndrome?

Answer 7

TGF-(B)

Question 8

Marian Syndrome clinical signs

Answer 8

Usually tall structure with exceptionally long extremities

Are usually double jointed in most joints

Can have a protruding (bossing) of the front skull.

Usually causes increased kyphosis and moderate scoliosis

Usually has pectas carinatum or excavatum

Almost always processes ectopic lens bilaterally.

Question 9

Most common cause of death in Marian syndrome

Answer 9

Aortic rupture of dissection in the cardiovascular system

• often shows mitral valve prolapse and congestive cardiac failure prior to rupture.

Question 10

Ehlers-Danlos syndrome characteristics

Answer 10

Defects in collagen synthesis and/or structure

• shows autosomal dominance and restive patterns
• affects a whole lot of types of collagen w/ six types being recognized (very heterozygous)

Question 11

Classic type of Ehlers-Danlos

Answer 11

Gene defects in COL5A1 & 5A2

Autosomal dominant inheritance

Clinical signs include:
-Extreme Skin and joint hypermobility, atrophic scarring and easy bruising.

Question 12

Vascular type of Ehlers-Danlos

Answer 12

Gene defect in COL 3A1

Autosomal dominant inheritance

Clinical signs include:
-Thin skin, arterial/uterine ruptures, baring, slight joint hyperextension

Question 13

Kyphoscoliosis Ehlers-Danlos

Answer 13

Gene defect in lysyl hydroxylase

Autosomal recessive inheritance

Clinical signs include: hypotonia of muscles, joint laxity, congenital scoliosis, ocular fragility.

Question 14

Systemic Sclerosis (Scleroderma) characteristics

Answer 14

Immunologic disorder that is caused by excessive fibrosis in tissues.

• show evidence of autoimmunity and production of these antibodies
• affects cutaneous tissue and visceral layers of the GI, lungs, heart and kidneys
• MOST COMMON FEATURE IS VERY OBVIOUS SKIN THICKENING
• women are 3x more likely than males to develop

Question 15

Diffuse systemic sclerosis

Answer 15

One group of systemic sclerosis

• characterized by initial widespread skin scaring with rapid progression towards visceral involvement

Question 16

Limited systemic sclerosis

Answer 16

One group of systemic sclerosis

• mild skin involvement and usually confided to fingers and face skin
• has late involvement of viscera if any

Question 17

CREST syndrome

Answer 17

Another way to say limited systemic sclerosis

Calcinosis 
Raynaud phenomenon (episodic vasoconstriction in extremities causing necrosis)
Esophageal dysmotility
Sclerodactyly 
Telangiectasia

Question 18

Causes of systemic sclerosis

Answer 18

Unknown (idiopathic)

• assumed to be caused by CD4 T-cells responding to unidentifed antigen and release cytokines which activates inflammatory cells and fibroblasts

Causes vascular damage and fibrosis from this autoimmune response (although again this is assumed)

Question 19

Systemic sclerosis skin morphology

Answer 19

Skin: fibrosis and atrophy beginning in fingers and moving proximally

• caused by edema and perivascular infiltrates via CD4 T-cells
• progression of disease is marked by increasing fibrosis of dermis.
• 100% of cases have skin affected

Question 20

Systemic sclerosis GI morphology

Answer 20

Progressive atrophy and fibrosis of GI musculature and usually begins in the esophagus

• inferior esophagus often looks like a rubber-hose and thin mucosa covering.

Dysphagia can be caused

• may produce ulceration, Barrett metaplasia and strictures.
• 90% of cases have affect GI tract

Question 21

Other possible systemic sclerosis morphology

Answer 21

Hypertension in kidneys

Pulmonary hypertension and interstitial fibrosis in lungs

Myocardial fibrosis and pericardial effusion in heart

Inflammation of synovial in musculoskeletal system

Question 22

Two ANAs that are strongly associated with Systemic Sclerosis

Answer 22

Anti-Scl 70 (DNA topoisomerase 1)
- causes pulmonary fibrosis

Anticentromere antibody
causes CREST syndrome