Genetic Diseases

Question 1

What kind of disease is Marfan syndrome (MFS)?

Answer 1

an inherited connective tissue disorder

Question 2

What causes MFS?

Answer 2

it has been considered caused by the deficiency of a structural extracellular matrix protein, fibrillin-1. Results from mutations in fibrillin-1 (FBN1) gene on chromosome 15, which encodes for glycoprotein fibrillin.

Involves dysregulation of the cytokine-transforming growth factor beta signaling.

Question 3

fibrillin

Answer 3

major building block of microfibrils, which constitute the structural components of the suspensory ligament of the lens and serve as substrates for elastin in the aorta and other connective tissues.

Question 4

Major criteria of MFS diagnosis

Answer 4

first degree relative who independently meets diagnostic criteria

presence of an FBN1 mutation known to cause Marfan syndrome

inheirtance of an FBN1 haplotype known to be associated with unequivocally diagnosed Marfan syndrome in the family.

in family members, major involvement in one organ system and involvement in a second organ system.

Question 5

clinical presentation of MFS

Answer 5

delayed achievement of gross and fine motor milestones secondary to ligamentous laxity of the hips, knees, ankles, arches, wrists and fingers

a decrescendo diastolic murmur from aortic regurgitation

am ejection click at the apex followed by a holosystolic high-poitched murmur from mitral prolapse and regurgitation

dysrhythmia

abrupt onset of thoracic pain

low back pain near tailbone, burning sensation and numbness or weakness in the les in serious dural ectasia

Question 6

Neurofibromastosis

Answer 6

complete penetrance
mildly affected patients show only cafe au lait macules, Lisch modules and axillary freckling. Dermal neurofibromas are frequenct and can be numerous and disf