Marfan and Ehlers-Danlos syndrome Flashcards
what is Marfan syndrome?
autosomal dominant connective tissue disorder affecting microfibrils and elastin in connective tissue throughout the body
associated with disorders of CVS, MSK system and eyes
what is Ehlers-Danlos syndrome?
heterogeneous group of connective tissue disorders with variable inheritance characterised by defective collagen synthesis and processing
pathogenesis of marfan syndrome
mutation of fibrillin-1 gene on chromosome 15 causing defective fibrillin
defective connective tissue microfibrils and defective elastin
inheritance of marfan syndrome
lots of different FBN1 mutations
autosomal dominant with variable penetrance
Ehlers-Danlos syndrome pathogenesis
defects in collagen caused by mutations in certain genes that control synthesis and processing of different types of collagen
inheritance of ehlers-danlos syndrome
inheritance patterns, severity and type of collagen affected vary
autosomal dominant or recessive
types of ehlers -danlos syndrome
there are 13 different types
most common types of ehlers-danlos syndrome
hypermobility
classical
classical-like
vascular
hypermobility ehlers-danlos syndrome
unknown genetic defect
unknown affected protein
joint instability - shoulder and patella dislocations
classical ehlers-danlos syndrome
COL5A1 and 2
type V collagen affected protein
joint and skin manifestations - generalised joint dislocations and easy bruising
classical-like ehlers-danlos
TNXB
Tenascin X
milder than classical type - joint hypermobility with fewer dislocations
Vascular
COL3A1
Type III procollagen
cardiovascular manifestations - mitral valve prolapse, aortic aneurysm and organ rupture
what body parts are affected by Marfan syndrome?
cardiovascular system
MSK system
skin
eyes
cardiovascular manifestations of marfan syndrome
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
berry aneurysms
rupture leads to subarachnoid haemorrhage
MSK manifestations of marfan syndrome
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
positive thumb sign
when thumb is placed in palm and fist clenched thumb extends beyond the ulnar border of the hand
positive wrist sign
when clasping wrist and thumb and little finger overlap
what is arachnodactyly
abnormally long, slender fingers and toes
pectus carinatum
sternal deformity where the middle and lower portions of the sternum protrude forward - aka sternal hyphosis
what is pectus excavatum?
sternal deformity where the middle and lower portions of the sternum protrude inward
pes planus
flat foot
spinal deformities in marfan syndrome
scoliosis
hyperkyphosis
skin manifestations of marfan syndrome
hyperextensive skin
striae - stretch marks
eye manifestations of marfan syndrome
visual impairment - ectopia lentis and lens subluxation severe myopia retinal detachment glaucoma early cataract formation
ectopia lentis
lens dislocation
superior and temporal lens subluxation
other manifestations of marfan syndrome
increased risk of spontaneous pneumothorax
lumbosarcal dural ectasia
types of manifestation in ehlers-danlos syndrome
cardiovascular MSK skin eyes other
CVS manifestations of ehlers-danlos syndrome
heart valve defects - mitral valve prolapse
cystic medial degeneration - aortic dilation, aneurysms or dissection
aneurysms/ dissections of iliac, splenic or renal arteries
berry aneurysms
MSK manifestations of ehlers-danlos syndrome
joint hypermobility with tendency towards dislocation
skeletal abnormalities
skin manifestations of ehlers-danlos syndrome
bruising easily skin hyperextensibility frequent lacerations of skin poor skin healing atrophic scars
eye manifestations of ehlers-danlos syndrome
myopia
retinal detachment and tears
other manifestations of ehlers-danlos
hernias
organ rupture causing pain and life-threatening internal bleeding
cervical insufficiency - uterine prolapse
dental abnormalities
dental abnormalities in ehlers-danlos syndrome
hypodontia
delayed eruption
molluscoid pseudotumors
diagnosis of marfan syndrome
clinical diagnosis genetic testing tests to identify specific manifestations echo slit-lamp examination of eye lens imaging - x-rays and MRI
diagnosis of ehlers-danlos
clinical diagnosis genetic testing tests to identify specific manifestations echo slit-lamp examination of eyes imaging - x-ray, MRI
Cystic medial degeneration
necrosis of large blood vessels, such as aorta
can lead to aortic dissection
Histopathology of cystic medial degeneration
loss, thinning, disorganisation and fragmentation of elastic tissue in tunica media
accumulation of mucoid extracellular matrix
loss of smooth muscle nuclei
treatment of marfan syndrome
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
Ehlers-danlos treatment
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
treatment of aortic dilatation
beta blockers
aortic root replacement surgery
treatment of scoliosis
bracing
surgery
marfan syndrome prognosis
normal life expectancy if diagnosed early and management of complications
careful monitoring required
aortic root disease is most common cause of death - aneurysm, dissection
ehlers-danlos syndrome
normal life expectancy in all types except vascular, in which it is approx. 50 years
