Heritable Connective Tissue Disorders

Question 1

overview of HCTD

Question 2

Genetic background for marfan syndrome

Answer 2

• single gene mutation (AUTOSOMAL DOMINANT) OF THE FBN1 (Fibrillin gene)
• affects MSK, ocular, cardiovascular
• life expectancy of 40-45, prognosis related to aortic complications

Question 4

clinical manifestations of Marfan syndrome

Answer 4

Question 5

how can you prevent the cardiac outcomes in someone with marfans

Answer 5

at the end of the day, most will live to 40-45 and die due to aortic rupture or ectopia lentis.BUT they should be on beta blockers or ARB, might need an aortic graft due to aortic root dilation.

Question 6

Ehlers Danlos Syndrome is a combination of 13 genetically heterogenous types of ___ diseases.

Answer 6

collagen diseases with vascular involvement–median age of death is 48 years.

Question 8

marfan syndrome investigations

Answer 8

Question 9

Outline the beighton scoring scale of EDS clinical manifestations

Answer 9

assesses hypermobility and dislocations. points are allocated depending on how many joints are hypermobile.

Question 10

most common clinical presentation in EDS.

• also, what skin features are noted in EDS?

Answer 10

most people are brought to the hospital due to hernias.

other clinical manifestations include piezogenic papules (fat herniations through fascia) and atrophic scarring, in addition to the stretchy fragile skin.

Question 11

vascular complications of EDS

Answer 11

• medium arterial dissection and rupture
• GI rupture (sigmoid colon most common site)
• pregnancy-related uterine rupture
• carotid cavernous fistula.

Question 12

caracterize the clinical presentations of Classic EDS, vEDS, and hEDS

Answer 12

Question 13

investigations of EDS

Answer 13

Regular labs
• CBC, Cre, Lytes, liver enzymes, assess for other
autoimmune diseases (ANA, CCP, RF)
• Annual ophthalmology exam

• First screening Echo for all EDS
• If normal q5years

• CTA or MRA if abnormalities or high suspicion • Medical genetics referral for Collagen gene testing
and counselling (except hypermobile EDS)

Question 14

EDS treatment

Answer 14

• education to prevent damage or CVS complications
• life style (refined low impact exercise programs, no gymnastics)
• physiotherapy to train joint proprioception
• occupational therapy for improved QOL and function
• orthotic bracing for dislocations
• pain management (FIBROMYALGIA management)
• joint arthroplasty for early oA

If vascular EDS: need surgical intervention for any vascular bleeding, beta blockers and ARB to control HTN, as well as desmopressin.

Question 15

outline the genetics behind achondroplasia

Answer 15

• single gene mutation (autosomal dominant) or the FGFR3 (fibroblast growth factor receptor 3 gene)

Question 16

achondroplasia is due to ___ dysplasia

Answer 16

physeal dysplasia; abnormal growth of physis

Question 17

achondroplasia pathophysiology

Answer 17

the mutation of the FGFR3 gene impacts Snail STAT and PP transcription factors, resulting in prevention of chondrocyte proliferation and differentiation

Question 18

main causes of premature death in someone with achondroplasia

Answer 18

spinal cord compression and complications, and heart disease.

Question 19

key pathognomonic ocular indication of marfan syndrome

Answer 19

ectopia lentis– diagnostic criteria, entire lens falls off to the bottom of the eye

Question 20