Marfan Syndrome

Question 1

What is the inheritence of Marfan syndrome?

Answer 1

Autosomal dominant

Question 2

Which type of systemic disease?

Answer 2

Connective tissue disorder

Question 3

Marfan syndrome: chromosome and gene

Answer 3

Chromosome 15

Gene: Fibrillin-1

Question 4

Other disorders associated with Fibrillin-1 mutation

Answer 4

Familial Ectopia lentis

Weill Marchesani syndrome

Question 5

Sex/gender of Marfan syndrome

Answer 5

both male and female are affected

Question 6

What is the carrier state?

Answer 6

NO carrier state

one mutated gene (heterozygote) will manifest disease

Question 7

Can Marfan syndrome skip a generation?

Answer 7

NO

normally appears in every generation

Question 8

Ratio of new mutation

Answer 8

Among the affected person, 25% are first affected/new mutation

Question 9

Arm span to body height ratio in Marfan syndrome

Answer 9

>1.05

Normal: <1.05

Question 10

Stature of Marfan syndrome

Answer 10

Tall stature with disproportionately long limbs (= dolichostenomelia)

Question 11

Intelligence in Marfan syndrome

Answer 11

Usually normal

Question 12

Eye features of Marfan syndrome

Answer 12

Ectopia lentis (superotemporal/upward lens dislocation)

Blue sclera

Myopia

Peripheral retinal degeneration >>> retinal detachment

Question 13

Head-neck features of Marfan syndrome

Answer 13

High arched palate ( & narrow)

Crowded teeth

High-arched neck

Question 14

Limb features of Marfan syndrome

Answer 14

Arachnodactyly

Steinberg sign positive

Walker-Murdoch sign positive

Joint laxity

Pes planus in foot

Question 15

Arachnodactyly

Answer 15

Also called ‘spider finger’

Arachnid = Spider

Fingers are abnormally long, slender, curved liked spider legs +

all or few fingers can be bent backwards of 180 degree

Question 16

What are the specific signs of Marfan’s syndrome?

Answer 16

Steinberg sign positive

Walker-Murdoch sign positive

Question 17

Steinberg sign

Answer 17

Fold your thumb >> then close your fist >> if thumb tip extends beyond the palm of hand >> Steinberg sign positive

Question 18

Walker-Murdoch sign

Answer 18

Grip your wrist with your opposite hand >>> if thumb and fifth finger of hand overlap with each other >>> positive Walker-Murdoch sign

Question 19

Radiological features of Marfan syndrome

Answer 19

Protrusio acetabulae

Dural ectasia in spinal MRI

Question 20

Trunk features in Marfan syndrome

Answer 20

Pectus Excavatum or Carinatum

Scoliosis >20degree

Question 21

Cardiac defects in Marfan syndrome

Answer 21

1. Dilation of the aortic root sinuses (90%cases of Marfan) >>> leads to Aortic regurgitation

2. Mitral valve prolapse (MVP) (75%cases of Marfan)

3. Aortic dissection

Question 22

The most common cardiac defect in Marfan syndrome

Answer 22

Aortic root dilation >>> leading to >>> Aortic regurgitation

Question 23

The second common cardiac defect in Marfan syndrome

Answer 23

Mitral valve prolapse (MVP) in 75% cases

often AR and MVP are present together

Question 24

Murmur of MVP (Mitral valve prolapse)

Answer 24

Late systolic murmur

Question 25

Pulmonary defect in Marfan syndrome

Answer 25

Repeated spontaneous pneumothoraces

Apical blebs on chest radiograph

Question 26

Skin feature in Marfan syndrome

Answer 26

Striae

Question 27

Blood defect in Marfan syndrome

Answer 27

Increased risk of thromboembolic disorder

Question 28

Similarity between marfan syndrom and homocystinuria

Answer 28

Marfan syndrome may present with high homocystine level (homocystinuria)

Homocystinuria may present with marfanoid habitus (e.g. arachnodactyly etc.)

Question 29

Difference between Marfan syndrome and homocystinuria

Answer 29

Marfan syndrome: Autosomal dominant

Homocystinuria: Autosomal recessive

Marfan syndrome: upward ectopia lentis

Homocystinuria: downward ectopia lentis

Question 30

Marfan syndrome is diagnosed by-?

Answer 30

Modified Ghent criteria

Question 31

Why did Ghent criteria need to be modified?

Answer 31

Due to emerging spectrum of mutations in fibrilin-1 associated disorders (other than Marfan syndrome)

Question 32

What is the significance of new modified Ghent criteria?

Answer 32

It placed greater weight on >>>

• Cardiac features
• Aortic dilatation
• Ectopia lentis

Question 33

How ‘systemic score’ is calculated to be used in modified Ghent criteria?

Answer 33

A systemic score is calculated, according to presence of >>>

• Musculoskeletal findings
• Radiological findings
• Skin findings

>> weighted according to their diagnostic specificity

Question 34

In patient without family history >> modified Ghent criteria to diagnose Marfan syndrome?

Answer 34

Any of the following four conditions >>> Diagnosis of Marfan syndrome:

• Aortic dilatation (Z score greater than or equalling 2) + Ectopia lentis
• Aortic dilatation (Z score greater than or equalling 2) + Fibrillin-1 gene mutation
• Aortic dilatation + systemic score greater than or equalling 7
• Ectopia lentis and Fibrilin-1 mutation

*** This Fibrillin-1 gene mutation should be known to be associated with Marfan syndrome, not other disorders

Question 35

In patient with family history >> modified Ghent criteria to diagnose Marfan syndrome?

Answer 35

Family history in first degree relatives = parent, siblings, child

If presence any of >>

• Family history + Aortic dilataion
• Family history + Ectopia lentis
• Family history + Systemic score greater than or equalling 7

>>>>> Dx of Marfan syndrome

Question 36

Treatment of Marfan syndrome

Answer 36

ACE inhibitors

Beta blockers

If lens is fully dislocated from pupil aperture >>>>> Aphakic lens

Question 37

Monitoring in Marfan syndrome

Answer 37

Regular echocardiography

Question 38

Life expectancy

Answer 38

Around 40 to 50years

If undiagnosed >>> high risk of death in 30s to 40s

Question 39

Main cause of death in Marfan syndrome

Answer 39

Aortic dissection (AD) & other heart defects