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Clinical Correlation 1 Collagen Pathologies - Coggle Diagram
Clinical Correlation 1 Collagen Pathologies
Marfan's Syndrome
Genetics
Epidemiology: Both males and Females; Phenotype more apparent w/ age
Diagnostics: skeletal abnormalities w/ family history of aortic aneurysm
Tests: Echocardiogram, x-ray, MRI, linkage analysis of FH
Inheritance: Autosomal dominant
2-3/10,000
Mut: Fibrillin 1 - elastin related :!:
Fibrillin 1 microfibers act as a scaffold for tropoelastin to make elastin fibers
Fibrillin 1 microfibers helps attaches BM to elastic fibers
Fibulin crosslink fibrillin and elastin subunits
Fibrillin loss increase transforming growth factor Beta
TGFB regulates proliferation and ECM deposition.
TGFB binds to receptor and receptor has serine/threonine kinase. It phosphorylates Smad2/3 which acts as a transcription factor.
Disease: Interstitial pulmonary fibrosis. TGF beta drives myofibroblasts proliferation and collagen deposition.
Marfanoid appearance
Symptoms
Thin, highly distensible skin :!:
Linear striae i.e. stretch marks
Eye: Ectopic lentis- upper displaced lens :!: :!!:
Myopia (near sight)
Mitral Valve prolapse: click btwn syst + diastole
Aortic root dilation
Long, narrow extremities w/ tall stature :!:
Arm span longer than height
Chest wall asymmetries: pectus excavatum, carinatum, etc
Arachnodactyly-long slender fingers: Shows thumb sign and wrist sign : :!:
Joint hyperextensibility
Respiratory: Blebs, bullae :!:
Predispose to spontaneous pneumothorax.
Treatment
Genetic testing and counselling
Monitor aorta/valvular abnormalities
Early valve replacement, beta blockers, or angiotensin receptor blockers.
Aortic root repair when diameter is 5cm or greater
Limit physical participation
Ehlers-Danlos Syndrome
6 subtypes
Type 1+2: Classical
Sx: joint instability
Inheritance: Autosomal dominant
Epidem: Both males and females; 1/5-20,000
Mut: Col5A1/Col5A2
Structure: Involved in the core of reticular fibers with Col3A1 surrounding it
Type 3: Hypermobility
Type 4: Vascular
Mutation in COL3A1/2
Sx: Muscles and Organs prone to rupture w/ easy bruising :!:
S/sx
MSK: Pes planus (flat feet)
MSK: Kyphosis and/or scoliosis
MSK Sx: Tendon sprain, freq joint dislocation/subluxation :!:
Sx: Less common: mitral valve prolapse and aortic valve dilation
Sx: Impaired healing
Diagnosis: Beighton score- mobility test; 9 criteria w/ 4 to establish hypermobility
Treatment: Physical therapy, manage pain, orthotics, Edu
Homocystinuria
Epidem: Males more often but both males and Fem.
1/100,000-300,000
More prevalent in Ireland
Diagnosis: Usually on state newborn screening labs. :star:
Unaffected at birth w/ progression if untreated
Diagnosis: Increased methionine and homocysteine in serum. Increased homocysteine in urine.
Treatment: Low protein (methionine) diet
Treatment: B6, B12, Folate, betaine supplementaiton
Folate given for pregnancy to assist in embryonic as well as general growth. Lack of it in child can harm CNS.
Treatment: IV cysteine supplementation to infants due to reduced methionine diet
Inherited disorder of methionine AA metabolism. :star:
Symptoms
Marfanoid body habitus
Osteoporosis
CNS: Developmental Delay/Intelectural disabilities :!!:
Seizures :!:
Myopia and Inferior Lens dislocation :!!:
Used to distinguish Marfan's and homocystinuria.
Thromboembolic disease- prone to embolism and MI. :!:
Fair complexion w/ sparse blonde hair
Hypopigmentation if dark skinned w/ vitilago pattern :!:
Livedo reticularis
Missing cystathionine Beta synthase to convert homocystein (methionine product) to cystathionine
B6 and B12 are necessary cofactors
Increased homocystein which is toxic.
Link
Inherit: autosomal recessive
Osteogenesis Imperfecta
Mutation: COL1A1 /2 defect
Epidem: Both males and females. Sx apparent from childhood.
Inherit: Autosomal dominant
Pop: 1/20,000
Types
Type 1 (mild)
Sx: Mild bone fragility w/ minimal fractures prior to walking; normal stature
Sx: higher risk of hearing loss and osteoporosis
Genetics: Null allele results in only 50% COL1A1/2 production
Type 2: lethal in utero or first yr of life :star:
Sx: Fractures present in utero
Short stature
Type 3-9: Moderate to severe
Sx: hearing loss and osteoporosis earlier in life
Short stature
Type 3 is the most severe that is compatible with life.
Dx: X-ray; dermal fibroblast culture
DDx: Child abuse, ricketts, osteomalacia
Treatment: Bisphosphonate treatment for moderate to severe forms (i.e. pamidronate w/ IV preferred)
Surgical repair as needed and physical therapy
Clinical Features
Blue/silver sclera :!:
Blue bc of choroid layer being exposed as a result of collagen deficiency.
Short stature
Dental imperfections
Hearing loss
1 Alpha Antitrypsin deficiency-Congenital disorder affecting lungs and liver. Elastin-related
Dx: Serum alpha 1 anti-trypsin level; gene seq; liver biopsy
Management: Pulmonary and routine liver fx testing w/ US. Check FH
Treatment: Avoid smoke, pulmonary rehab, IV A1AT (to slow progress), and liver/lung transplant
Genetics
Serpina1 mutation
Decreased/absent alpha 1 antitrypsin results in increased neutrophil elastase which breaks down elastin and affects the lungs -->COPD :!:
Epidem: Males and Females; child w/ cholestasis and poor growth; young patient w/ emphysema +/- cirrhosis
Inherit: Autosomal dom (co-dom)
80,000-100,000
Symptoms
Young pt w/ emphysema in non-smoker :!:
Sx: Blebs located more inferior in lungs.
Sx: Adult w/ cirrhosis :!:
Portal hypertension w/ esophageal varices
Jaundice
Hepatocellular carcinoma
Decreased syn of coagulation factors
Biopsy: Z alpha anti trypsin (ZAAT) misfolded in liver resulting in inclusion bodies in hepatic ER to cirrhosis
Sx: Panniculitis (inflam of subcut fat)
Sx: Child w/ cholestasis or poor growth