CIS

Question 1

Marfan

Answer 1

fibrillin gene defects (FBN1) that leads to excessive TGF-beta expression and defective elastin fibers (loss of function defect- haploinsufficiency) that mimics a dominant negative effect

key: armspan greater than height

once incorrectly thought to be a dominant negative mutation

treatment: Losartan Rx (angiotensin II, type 1 receptor antagonist that blocks AT1 action on TGF-beta stimulation of ERK, which is what actually drives growth)

Mutations in the TGF-beta receptors give rise to a similar syndrome called Loeys-Dietz syndrome

Question 2

stickler

Answer 2

looks like marfans but short

Question 3

MASS phenotype

Answer 3

Mitral valve prolaps
Aortic root diamteter big
Skin may show stretch marks
Skeletal features- incl. scoliosis

Question 4

most common leukemia with trisomy 21

Answer 4

ALL is the most common

AML with megakaryocytic maturation is the most common myeloid leukemia

AMkL is 90% of AML cases in Down syndrome patients– 500x more common than in overall population
ALL is 20x more common than overall population

but the numbers of AML are super low to begin with.

Question 5

Gaucher disease

Answer 5

mutations in glucocerebridase

Type II: infantile acute cerebral pattern

Question 6

vitamin D deficiency and clinical findings

Answer 6

Rickets; Vitamin D; bowlegged

• Rachitic rosary
• Called osteomalacia in adults; bone breakdown with micro-fractures, looks like osteoporosis

Question 7

Loeys-Dietz

Answer 7

marfanoid

mutation in TGF-B receptor