MSKS Pathology Lecture 2_CT Diseases

Question 1

What is Raynaud’s phenomenon and how prevelent is it in systemic sclerosis

Answer 1

see attached

Question 2

In addition to bone, what other tissues are affected by osteogenesis imperfecta?

Answer 2

joints, eyes, ears, skin, teeth.

Question 3

Systemic Sclerosis is charicterized by what?

Answer 3

see attached

Question 4

Where are microfibrils most abundent (aka the areas most effected by Marfan Syndrom?)

Answer 4

aorta, ligaments, and the ciliary zonules that support the lens

Question 5

Non functional microfibrils lose the ability to sequester what? what effect does this have?

Answer 5

They lose the ability to sequester Transforming Growth Factor-beta (TGF-beta). This has a deleterious effects on vascular smooth muscle development and the integrity of extracellular matrix

Question 6

What demographic is most at risk for systemic sclerosis?

Answer 6

Women between the ages of 50 and 60

Question 7

What is the prognosis for type 2 ostiogenesis imperfecta?

Answer 7

uniformly fatal in utero or during the perinatal period

Question 8

What is the most common osteogenesis imperfecta? What is its prognosis

Answer 8

Type 1 OI is the most common. It has the best prognosis. Individuals have normal life spans and stature.

Question 9

What causes fibrosis in systemic sclerosis?

Answer 9

See attached

Question 10

How many recongnized varients of EDS are there?

Answer 10

6

Question 11

Marfan syndrome is characterized by changes on what systems?

Answer 11

skeleton, eyes, and cardiovascular systems

Question 12

What are some charicteristics of EDS?

Answer 12

joints are hypermobile, skin is extraordinarily stretchable, extremely fragile, and vulnerable to traumaserious internal complications, e.g., rupture of the colon and large arteries

Question 13

Mutations in which genes cause ostiogenesis imperfecta?

Answer 13

COL1A1 and COL1A2

Question 14

Osteogenesis imperfecta is caused by the lack of sysnthesis of what?

Answer 14

Type 1 collagen

Question 15

Mutations that cause ostiogenesis imperfecta typically replace which amino acid?

Answer 15

Typically replaces glycine with something else. This disrupts hydrogen bonding between the alpha chains. Although, other mutations can simply result in decreased synthesis of normal collagen molecules.

Question 16

What two ANAs are strongly associated with Systemic Sclerosis

Answer 16

One directed against DNA topoisomerase and an anticentromere antibody

Question 17

Mutations in which gene cause Marfan syndrome?

Answer 17

FBN1 (there are over 1800 known mutations. This is because FBN1 is a very large gene)

Question 18

What is Ehlers-Danlos Syndromes

Answer 18

group of diseases characterized by defects in collagen synthesis or structure

Question 19

What is the prevelance of Marfan syndrome? What is it’s inheritance pattern? What percentage of cases are genetically inherited?

Answer 19

1 in 5000. It is Autosomal dominant and 70-85% of cases are inherited. The rest arise from new mutations.

Question 20

What is the most common cause of death in marfan syndrome?

Answer 20

Aortic rupture is the most common cause of death

Question 21

Marfan syndrome is a defect in which extracellular glycoprotein. What is this extracellular glycoprotein important for?

Answer 21

fibrillin-1, a major component of micofibrils (elastic fibers)

Question 22

What is the most common inherited disorder of connective tissue?

Answer 22

Osteogenesis Imperfecta

Question 23

What is the molecular basis for the three most common variants of EDS

Answer 23

✴ Deficient synthesis of type III collagen resulting from mutations affecting the COL3A1 gene.* ✴ Deficiency of the enzyme lysyl hydroxylase.** ✴ Deficient synthesis of type V collagen.***

Question 24

In addition to bone fragility, what other three clinical finding can ostiogenesis imperfecta have?

Answer 24

Blue sclerae, Hearing loss (because bones of the ear are compromised), and Dental imperfections