Inherited disorders of connective tissue (Ehlers-Danlos, Marfan) Flashcards
Define Ehlers-Danlos syndrome.
Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders. They are caused by pathogenic variants affecting genes encoding for, or modifying, collagen, fibrillin, and/or other matrix proteins.
What are the clinical features of EDS?
Ehlers–Danlos syndrome
- MSK
- Joint hypermobility
- Joint or spine pain - no signs of inflammatory joint disease, no restriction
- Motor delay in infancy
- Fatigue
- Recurrent joint dislocation/subluxation
- Muscle pain/spasms
- Marfanoid habitus
- Derm:
- Soft, silky skin texture
- Semi transparent skin
- Stretchy skin on dorsum of hand
- Striae
- Poor wound healing
- Easy bruising
- Hernias
- Cardiac:
- Mitral valve prolapse
- Aortic aneurysm
- Aortic dissection
- Orthostatic hypotension and POTS
- GI bleeds.
Which feature of EDS is shown?
Translucent skin
Which feature of EDS is shown?
Atrophic healing of scars due to collagen deficiency
How is EDS classified?
There are 13 types which can be AD or AR with different associated genes
Also called hypermobility spectrum disorder
What is the aetiology of EDS? What is the usual inheritance pattern?
Genetic mutation in one or more genes encoding collagen or proteins that interact with collagen e.g. tenascin. Specific genes lead to specific risks e.g. skin pathology or vascular pathology.
Hypermobile EDS is AD inheritance
Usually autosomal dominant
Most affected people do not develop symptoms at all
What investigations are used for diagnosis of EDS?
Clinical diagnosis
Beighton 9-point score - 5 or higher indicates hypermobility. Apart from joint hypermobility, no feature is universally present in any form of EDS
Brighton criteria
Genetic testing - can be done only for mutations which are mapped. Prenatal diagnosis may be offered where multiple family members are affected
What is the management of EDS?
- Avoid contact sports - risk of bone and tissue injury
- Genetic couselling
- Pain management - simple analgesia, corticosteroid injections, NSAIDs, othr fibromyalgia treatments.
- Physiotherapy
- Splints/orthotics - for joint dyslocation, although NB: the best splint is the patient’s own musculaure
What are the components of the Brighton criteria?
Major Criteria
- Beighton ≥4/9
- Arthralgia ≥3 months , ≥ 4 joints
Minor Criteria
- Beighton score 1-3/9
- Arthralgia (> 3 months) in one to three joints or back pain
- spondylosis, spondylolisthesis.
- Dislocations/subluxations
- Soft tissue rheumatism > 3 lesions
- Marfanoid habitus
- Abnormal skin
- Eye signs
- Varicose veins or hernia or uterine/rectal prolapse
2 major criteria,1 major and 2 minor criteria, 4 minor criteria, or 2 minor criteria and the presence of an unequivocally affected first-degree relative
How is POTS diagnosed?
Tilt-table test - 30bpm or more increase in pulse on standing OR >120 within 10min of head-up
How is orthostatic hypotension diagnosed?
>20 mmHg drop in blood pressure on standing
(>25 mmHg drop in blood pressure is indicative of neurally mediated hypotension (NMH))
What are the complications of EDS?
Degenerative arthritis - if steps are not taken to reduce joint instability
Other type-specific risks (esp in vascular EDS)
- Large or medium-sized arteries, intestines, uterus, and/or tendons can spontaneously rupture or tear
- Surgery related complications
- Pregnancy complications
Define Marfan syndrome.
Marfan syndrome = AD inherited disorder of connective tissue, characterised by loss of elastic tissue, affecting numerous body systems, including the:
- MSK,
- cardiovascular,
- neurological,
- and respiratory systems,
- and the skin and eyes
What is the criteria for Marfan syndrome diagnosis?
The essential simplified criteria for diagnosis are 3 out of the 4 following findings:
- relevant family history,
- specific musculoskeletal abnormalities,
- high arched palate,
- scoliosis,
- pectus excavatum,
- flat feet,
- arachnodactyly with positive thumb sign,
- dolichostenomelia (long limbs) with increased arm span
- high level of pubic bone
- ocular lens subluxation,
- aortic dilation/dissection.
Skin striae, dural ectasia, hernias, pneumothorax, and emphysematous bullae on CXR may also be noted.
What are the clinical features of Marfan syndrome?
- MSK/physical:
- Tall stature
- Wide arm span
- High level of pubic bone
- High arched palate
- Arachnodactyly
- Positive wrist sign - distal phalanges of the first and fifth digits of the hand overlap when wrapped around the other wrist.
- Positive thumb sign - shown
- Pectus excavatum or carinatum - sternum sunk or pushed out respectively
- Scoliosis
- Pes planus
- Joint hypermobility
- Dental crowning
- Low back ache
- Joint pain
- Derm:
- Hernias
- Striae
- Ophthalmic:
- Dislocated/subluxed eye lens
- Myopia +/- astigmatism
- Retinal abnormalities
- Glaucoma - open-angle most common
- Cardiorespiratory:
- Aortic valve and mitral valve murmur
- Spontaneous pneumothorax
What is shown?
Positive thumb sign in Marfan syndrome
How do you calculate the Beighton score?
4 or more indicates hypermobility - each side is 1 and touching floor is 1
What is shown?
Piezogenic papules - SC fat that appears on standing
What test is shown?
Steinberg sign - found in Marfan syndrome which has many typical hand characteristics
What sign is shown?
Walker-Murdoch sign - Marfan’s
Which hypermobility syndrome is shown on the left vs right?
Hypermobile EDS (left)
Classical EDS (right)
Which hypermobility syndrome is shown on the left vs right?
Vascular EDS (left)
Classical-like EDS (right)
