Connective Tissue Disorders

Question 1

Marfan Skeletal Phenotype

Answer 1

-arachnodactly
-scoliosis
-pectus
+increases risk for pneumothorax
-tall stature
-abnormally large wingspan (>2x height)
-joint hyper mobility
+increased risk for degenerative arthritis
-pes planus

Question 2

Marfan Genetics

Answer 2

-AD inheritance of FBN1 mutation
+near 100% penetrance with similarities in family members that share same genotype
+25% de novo
-example of pleiotropy
-incidence of 1 in 5000-10000, no sex or ethnicity bias

Question 3

Marfan diagnosis

Answer 3

-fits certain clinical criteria
-genetic sequencing of associated gene
+sometimes a need for del/dup

Question 4

Marfan management

Answer 4

-prophylactic aortic surgery
+valve sparing is SoC
-prophylactic beta blocker or angiotensin receptor blocker prescription
-routine bone screening to measure density by adulthood

Question 5

Additional Marfan Features

Answer 5

-ectopia lentis, near sightedness and blue sclera
-dural ectasia (especially in sacral region)
-TAA and TAAD
+aorta 3x nL with aortic valve dysfunction; thinning of aortic wall, expanding diameter
+MVP
+sometimes CM
+predisposition to SCD due to fragmentation of cardiac elastic fibers

Question 6

EDS diagnosis

Answer 6

• meets clinical criteria on Brighton scale

- sometimes genetic confirmation useful

Question 7

EDS genetics

Answer 7

-failure of synthesis or cross-linkage of collagen
-6 subtypes caused by mutations of COL_A genes mostly, also sometimes TNXB, PLOD1
+Type I-IV AD, Type V-VI

Question 8

EDS phenotype

Answer 8

-hypermobility
-easy bruising, soft stretchy skin and cigarette paper scars
-easy dislocations
-chronic pain
+in some cases can have life-threatening rupture of blood vessels and organs with dysmorphic features