Marfan Syndrome

Question 1

Genetic Cause Marfan Syndrome

Answer 1

1. autosomal dominant
2. mutation in FBN1 gene
   - encodes fibrillin-1

Question 2

Normal function fibrillin-1

Answer 2

1. regulates growth and repair of various body tissues
2. combines with other structural proteins to form microfibrils
   - microfibrils= lend strength and flexibility to all connective, load bearing tissues

Question 3

microfibrils

Answer 3

lend strength and flexibility to all connective, load bearing tissues

formed from fibrillin-1 and other proteins

Question 4

FBN1 location

Answer 4

chromosome 15q21.1

Question 5

FBN1 mutation

Answer 5

1. autosomal dominant
2. creates abnormal protein
   (fibrillin 1 protein)
3. mutations vary widely among affected families, and are scattered across the gene (genetic heterogeneity)

Question 6

Genetics marfan syndrome

Answer 6

1. penetrance FBN1 mutation= 100%
2. variable expressivity and severity sx
3. autosomal dominant

Question 7

Loeys-Dietz syndrome

Answer 7

different genotype, TG(beta)R2- receptor protein if TGF-beta mutation

-offers same phenotype to marfan’s

Question 8

Genocopy

Answer 8

genotype that determines a phenotype which closely resembles the phenotype determined by a different genotype

Question 9

Dx marfans

Answer 9

1. based on family history and
   a. aortic dilation/dissection at level of sunrises of valsalva
   b. ectopia lentis
   c. presence of systemic features

Question 10

Marfan’s genetic testing and counseling

Answer 10

1. genetic testing for FBN1
   - component of clinical dx
   - prenatal dx
   - predictive testing in families with known mutation
2. clinical eval
   - medical hx
   - family hx
   - echocardiogram
3. linkage analysis/genetic studies for families in which FBN1 mutation has been previously identified

Question 11

Management marfan’s

Answer 11

1. CV surveillance
   - annual echocardiogram
   - more frequent if aortic root diameter is enlarges or there is aortic regurgitation
2. avoid
   - contact sports
   - isometric exercise
   - caffeine
   - decongestant
   - breathing against resistance (brass instrument)
   - negative pressure ventilation (scuba diving)
3. lower BP pharmacologically
   - protect aorta
4. surgical repair aorta, retina, breastbone
5. correction scoliosis