Connective tissue disorders Flashcards
Benign Joint Hypermobility Syndrome (BJHS) - outline DDx, Beighton’s criteria & other minor criteria
BJHS involves hypermobility of the joints, including the ability to hyperextend at the knees, elbows & MCP joints, or hyperflex at the hips & thumb
(à Beighton score). Combined with other minor criteria such as:
Chronic - greater than 3 months, arthralgia (>3 joints) or back pain.
Spondylosis, dislocation/subluxation in more than one joint.
Soft tissue rheumatism - > 3 lesions (e.g. epicondylitis, tenosynovitis, bursitis)
Marfanoid habitus (tall, slim, span/height ratio >1.03, upper: lower segment ratio less than 0.89, arachnodactyly)
Abnormal skin: striae, hyperextensibility, thin skin, papyraceous scarring.
Eye signs: drooping eyelids or myopia or antimongoloid slant.
Varicose veins or hernia or uterine/rectal prolapse.
BJHS is excluded by presence of Marfan or Ehlers-Danlos syndromes (other than the EDS Hypermobility type ).
The Beighton Score is used to assess children for joint hypermobility. The maximum possible score is 9.A score of 4 or more indicates joint hypermobility.
Place the hands flat on the floor without bending the knees (1 point.)
Oppose the thumb to the volar aspect of the ipsilateral forearm (1 point for right and 1 for left.)
Passively dorsiflex the fifth metacarpophalangeal joint by at least 90 degrees (1 point for right and 1 for left.)
Hyperextend the knee by at least 10 degrees (1 point for right and 1 for left.)
Hyperextend the elbow by at least 10 degrees (1 point for right and 1 for left.)
Ehlers-Danlos syndrome. - define, outline features & treatment
Ehlers-Danlos syndrome.
This is a group of genetically heterogeneous connective tissue disorders.
Genes that encode for collagen or for enzyme in collagen synthesis process
Pathophysiology: defective collagen synthesis
Type 1 - skin, tendons, organs & bones
Type 2 - cartilage (joints)
Type 3- reticular fibers (soft tissue support matrix)
Type 4 - basal lamina of epithelium
Type 5 - cell surface, hair, placenta, & (type 1 structures)
Genes: ‘COL- (collagen)’ ‘5 (type)’ ‘alpha chain (1 or 2)’
- Gene transcription forms preprocollagen
- Undergoes hydroxylation (enzymes add -OH groups onto proline & lysine)
- Glycosylation
- 3x chains then twists into triple helix (pro-collagen)
- Proteolytic processes, cleave loose ends (peptidases)
- Cross linking -> bind together fibrils
Affected children appear normal at birth, but skin hyperelasticity, fragility of the skin and blood vessels, delayed wound healing, and joint hypermobility develop.
6 clinical forms:
- classical (CEDS)- COL5A1/2 - autosomal dominant CLEDS -TNXB)
- hypermobile (HEDS- 90%) - no genetic mutation identified
- vascular (VEDS) COL3A1- weakens blood vessels
- kyphoscoliosis (KEDS)- autosomal recessive- impaired hydroxylation
- arthrochalasia (AEDS) - COL1A/2A
- dermatospraxis (ADMTS2)
Confirm diagnosis with genetic studies
Supportive treatments only
Marfan syndrome
Marfan syndrome
Genetic syndrome affecting connective tissue
Genetics: Autosomal dominant, FBN-1 chromosome 15
- Heterozygote : dysfunctional/reduced fibrillin-1
- Homozygote:
Pathogenesis: abnormal production in fibrillin-1
- Provide tissue integrity/connective tissue -> tendons, ciliary zonules in eye
- Forms scaffold for elastin (provides elastance) -> arteries, skin & lungs
- Also decreases TGF-B to reduce growth
= low tissue elasticity & integrity, increased growth
Tall individuals (Marfenoid body habitus) -> excessive long bone growth
- Hypermobile joints
- Arachnodactly
- Pectus excavatum/carinatum
- Scoliosis
- Narrow palate
Skin
- Stretch marks
- Bullae
Eyes
- Retinal detachment
- Lens dislocation
Heart
- Cystic medial necrosis
- Aortic valvular insufficiency/MVP
- Risk of dissection/aneurysm
Clinical diagnosis
Features: >2 + of more (may present as child grows) , FHx & FBN-1 mutation
Treatment (symptomatic)
- Artificial lens
- Losartan (ARB: slows TNF-B signalling), B-blocker, valvular repair
