Inherited connective tissue disorders Flashcards
Examples of inherited connective tissue disorders?
- Marfan syndrome
- Ehlers-Danlos syndrome (EDS)
- Osteogenesis imperfecta
Epidemiology of Marfan syndrome
Female = male
75% of cases have a family history & 25% are new mutations.
Aetiology and pathophysiology of Marfan syndrome
Autosomal dominant inheritance.
Caused by mutations in fibrillin-1 gene, which results in an abnormal fibrillin protein.
- This causes mechanical instability & abnormal elastic properties of the connective tissue so parts of the body can stretch abnormally.
- Fibrillin gene also causes bones to grow longer
NOTE: fibrillin is found in the elastic fibres which are a constituent of connective tissue.
Clinical presentations of Marfan syndrome
- Joint hypermobility
- Tall stature & wide arm span
- Aortic or mitral valve murmur or aortic anyeurism.
- Pectus excavatum - funnel chest.
- Pectus carinatum - pidgeon breast.
- Scoliosis
- Flat feet - pes planus.
- High arched palate - may lead to dental crowding.
- Dislocated or subluxed eye lens
- Myopia & astigmatism - i.e. shortsightedness & imperfect curvature of the eye causing blurred distance vision.
- Arachnodactyly - long, slender fingers (confirmed by positive thumb & wrists signs).
Positive thumb sign
- Thumb goes over fingers when making a fist.
Positive wrist sign
- Distal phalanges of the first & fifth digits of the hand overlap when wrapped around the other wrist.
NOTE: view images on notes
Investigation for Marfan syndrome
1st line:
- ECG, thorax CT or MRI - used initially for aortic root imaging.
- Abdominal ultrasound, CT or MRI - used to identify the descending aorta.
- Family history
2nd line:
- Blood screen for fibrillin-1 gene
- Lower spine MRI or CT can exclude dural ectasia (lower spinal membrane swelling). This is a complication of Marfan syndrome & Ehlers Danlos.
Ghent criteria:
- consists of major and minor criteria
- If you have a family history of Marfan syndrome, you’ll need to have 1 of the major criteria & 1 of the minor criteria.
- If you do not have a family history of Marfan syndrome, you’ll need to have 2 major criteria & 1 of the minor criteria.
Major criteria- features common in people w/ Marfan syndrome that are rare in people who do not have it.
- e.g. an enlarged aorta, a tear in the aorta, a family history of the syndrome, at least 4 skeletal problems, such as flat feet or a curved spine (scoliosis)
Minor criteria- features present in people w/ Marfan syndrome, but also present in people who do not have it.
- E.g. short sightedness, stretch mark, high palate
Management of Marfan syndrome
No cure for Marfan syndrome, so management involves screening & fixing issues caused by the disease
Aortic dilation
- urgery or beta blockers if surgery isn’t indicated.
Retinal tear
- Laser photocoagulation or surgery
Myopia
1st line: Glasses
2nd line: surgery
Lens subluxation
- 1st line: Glasses
- 2nd line: Surgery
Scoliosis
- 20-40° curves: orthopaedic bracing
- Larger curves: surgical correction & spinal fusion
Pathophysiology of Ehlers- Dandlos syndrome
Autosomal dominant
Classical EDS = affects type 5 collagen= resulting in easy bruising, joint & cardiac defects.
Vascular EDS= affects type 3 collagen= can cause blood vessels to rupture results in hyper mobility
NOTE: similar features to Marfan
Clinical presentation of Ehlers- Dandlos syndrome
Summed up by someone who’s skin & joints are very malleable & has chronic muscle pain.
MSK:
- Joint hypermobility
- Joint or spine pain
- Recurrent joint dislocation or subluxation
- Muscle pain and/or muscle spasm
- Motor delay in infancy
- Chronic pain syndrome
- Kyphoscoliosis- type VI
Skin:
- Skin hyperextensibility - thin & stretchy double fold of skin
- Atrophic scars - an indented scar that heals below the normal layer of skin.
- Easy bruising
- Poor wound healing and/or wound dehiscence
- semi-transparent skin
NOTE: view notes for images
Investigations for Ehlers- Dandlos syndrome
- Clinical diagnosis through patient history
- Family history
- Genetic testing - mutation of type 3 & 5 collagen gene
Management for Ehlers- Dandlos syndrome
Pain management e.g. NSAIDs, skeletal relaxents, opiod analgesics. & Corticosteroid injections
Genetic counselling - explain pattern of inheritance (because this is autosomal dominant, child has 50% of inheriting disease).
Physiotherapy & occupational therapy - restores range of movement.
Splints & orthotics
CBT
Avoid aspirin & NSAID- affect platelet function & clotting
- can lead to Reyes sydrome
- interacts w/ fatty acid metabolism causing ammonia and effects brain & causes it to swell & effects the skull compresses brain and spinal chord etc.- V IMPORTANT- LEARN
BETA blockers may reduce aortic dilation
Prognosis for Ehlers- Dandlos syndrome
- Only vascular EDS results in a shortened lifespan of 51 years.
- Pregnancy is hazardous but can be successful.
- CBT to help w/ pain improves the patients quality of life.
Pathophysiology of osteogenesis Imperfecta
Caused by an autosomal dominant mutation in the gene coding for type 1 collagen
-Results in brittle bones
7 main types - with type 1 being mildest & 2 being the worst.
Clinical features of osteogenesis imperfecta
- Lots of fractures at a young age w/out major trauma.
- Deformed stature (short)
- Scoliosis
- Brittle teeth
- Deafness
- Blue sclera- white part of eyes turn blue
commonly confused w/ NAI
NOTE: view notes for images
Investigation for osteogenesis imperfecta
- X-rays to identify abnormal bone structure
- DEXA scan
- Hearing and physical exam
- Family history
Management for osteogenesis imperfecta
- treat symptoms as there’s no cure.
- Surgical & dental procedures are commonly required.
- Mobility aids e.g. wheel chairs can be used with people that have the most severe forms of OI.
