Marfan and Ehlers-Danlos syndrome

Question 1

what is Marfan syndrome?

Answer 1

autosomal dominant connective tissue disorder affecting microfibrils and elastin in connective tissue throughout the body
associated with disorders of CVS, MSK system and eyes

Question 2

what is Ehlers-Danlos syndrome?

Answer 2

heterogeneous group of connective tissue disorders with variable inheritance characterised by defective collagen synthesis and processing

Question 3

pathogenesis of marfan syndrome

Answer 3

mutation of fibrillin-1 gene on chromosome 15 causing defective fibrillin
defective connective tissue microfibrils and defective elastin

Question 4

inheritance of marfan syndrome

Answer 4

lots of different FBN1 mutations

autosomal dominant with variable penetrance

Question 5

Ehlers-Danlos syndrome pathogenesis

Answer 5

defects in collagen caused by mutations in certain genes that control synthesis and processing of different types of collagen

Question 6

inheritance of ehlers-danlos syndrome

Answer 6

inheritance patterns, severity and type of collagen affected vary
autosomal dominant or recessive

Question 7

types of ehlers -danlos syndrome

Answer 7

there are 13 different types

Question 8

most common types of ehlers-danlos syndrome

Answer 8

hypermobility
classical
classical-like
vascular

Question 9

hypermobility ehlers-danlos syndrome

Answer 9

unknown genetic defect
unknown affected protein
joint instability - shoulder and patella dislocations

Question 10

classical ehlers-danlos syndrome

Answer 10

COL5A1 and 2
type V collagen affected protein
joint and skin manifestations - generalised joint dislocations and easy bruising

Question 11

classical-like ehlers-danlos

Answer 11

TNXB
Tenascin X
milder than classical type - joint hypermobility with fewer dislocations

Question 12

Vascular

Answer 12

COL3A1
Type III procollagen
cardiovascular manifestations - mitral valve prolapse, aortic aneurysm and organ rupture

Question 13

what body parts are affected by Marfan syndrome?

Answer 13

cardiovascular system
MSK system
skin
eyes

Question 14

cardiovascular manifestations of marfan syndrome

Answer 14

aortic disease
aortic necrosis - weakening of the elastic artery
aortic aneurysm
thoracic or abdominal aortic aneurysm
aortic root dilation - aneurysm of the proximal thoracic aorta
aortic regurgitation
aortic dissection - typically thoracic aorta
mitral valve prolapse
berry aneurysms

Question 15

berry aneurysms

Answer 15

rupture leads to subarachnoid haemorrhage

Question 16

MSK manifestations of marfan syndrome

Answer 16

tall stature
long extremeties 
joint hypermobiltiy - positive wrist and thumb signs 
high-arched palate 
arachnodactyly 
pectus deformity 
pectus carinatum 
pectus excavatum 
pes planus 
spinal deformities 
vertical overdevelopment of head 
winged scapula
habitual dislocations 
acetabular protrusion

Question 17

positive thumb sign

Answer 17

when thumb is placed in palm and fist clenched thumb extends beyond the ulnar border of the hand

Question 18

positive wrist sign

Answer 18

when clasping wrist and thumb and little finger overlap

Question 19

what is arachnodactyly

Answer 19

abnormally long, slender fingers and toes

Question 20

pectus carinatum

Answer 20

sternal deformity where the middle and lower portions of the sternum protrude forward - aka sternal hyphosis

Question 21

what is pectus excavatum?

Answer 21

sternal deformity where the middle and lower portions of the sternum protrude inward

Question 22

pes planus

Answer 22

flat foot

Question 23

spinal deformities in marfan syndrome

Answer 23

scoliosis

hyperkyphosis

Question 24

skin manifestations of marfan syndrome

Answer 24

hyperextensive skin

striae - stretch marks

Question 25

eye manifestations of marfan syndrome

Answer 25

``` visual impairment - ectopia lentis and lens subluxation severe myopia retinal detachment glaucoma early cataract formation ```

Question 26

ectopia lentis

Answer 26

lens dislocation | superior and temporal lens subluxation

Question 27

other manifestations of marfan syndrome

Answer 27

increased risk of spontaneous pneumothorax | lumbosarcal dural ectasia

Question 28

types of manifestation in ehlers-danlos syndrome

Answer 28

``` cardiovascular MSK skin eyes other ```

Question 29

CVS manifestations of ehlers-danlos syndrome

Answer 29

heart valve defects - mitral valve prolapse cystic medial degeneration - aortic dilation, aneurysms or dissection aneurysms/ dissections of iliac, splenic or renal arteries berry aneurysms

Question 30

MSK manifestations of ehlers-danlos syndrome

Answer 30

joint hypermobility with tendency towards dislocation | skeletal abnormalities

Question 31

skin manifestations of ehlers-danlos syndrome

Answer 31

``` bruising easily skin hyperextensibility frequent lacerations of skin poor skin healing atrophic scars ```

Question 32

eye manifestations of ehlers-danlos syndrome

Answer 32

myopia | retinal detachment and tears

Question 33

other manifestations of ehlers-danlos

Answer 33

hernias organ rupture causing pain and life-threatening internal bleeding cervical insufficiency - uterine prolapse dental abnormalities

Question 34

dental abnormalities in ehlers-danlos syndrome

Answer 34

hypodontia delayed eruption molluscoid pseudotumors

Question 35

diagnosis of marfan syndrome

Answer 35

``` clinical diagnosis genetic testing tests to identify specific manifestations echo slit-lamp examination of eye lens imaging - x-rays and MRI ```

Question 36

diagnosis of ehlers-danlos

Answer 36

``` clinical diagnosis genetic testing tests to identify specific manifestations echo slit-lamp examination of eyes imaging - x-ray, MRI ```

Question 37

Cystic medial degeneration

Answer 37

necrosis of large blood vessels, such as aorta | can lead to aortic dissection

Question 38

Histopathology of cystic medial degeneration

Answer 38

loss, thinning, disorganisation and fragmentation of elastic tissue in tunica media accumulation of mucoid extracellular matrix loss of smooth muscle nuclei

Question 39

treatment of marfan syndrome

Answer 39

``` no causal treatment treatment of specific symptoms and manifestations physical therapy analgesia treat scoliosis, aortic dilatation regular check ups ARBs and beta blockers to lower BP ```

Question 40

Ehlers-danlos treatment

Answer 40

``` no causal treatment treatment of specific symptoms and manifestations physical therapy analgesia treat scoliosis, aortic dilatation regular check ups avoid high contact sports surgery performed with caution to avoid excessive bruising and internal bleeding ```

Question 41

treatment of aortic dilatation

Answer 41

beta blockers | aortic root replacement surgery

Question 42

treatment of scoliosis

Answer 42

bracing | surgery

Question 43

marfan syndrome prognosis

Answer 43

normal life expectancy if diagnosed early and management of complications careful monitoring required aortic root disease is most common cause of death - aneurysm, dissection

Question 44

ehlers-danlos syndrome

Answer 44

normal life expectancy in all types except vascular, in which it is approx. 50 years