Exam #3: Genetic Disorders Flashcards
What is the definition of an autosomal dominant disorder?
- Person has one good gene, where most have two
- Makes 50% as much of the normal protein
What are the four categories of autosomal dominant disorders?
1) Quantity or arrangement of large structural proteins
2) Regulator proteins & receptors
3) Deficiency in proteins that are normally in low supply
4) Anti-oncogene deletion syndromes
What are the chances of an affected parent passing on an autosomal dominant disorder?
50% chance of either sex being affected
**Does NOT skip generations
What is reduced penetrance?
Condition in which the individual has the genetic mutation but does not have outward symptoms of disease
What is variable expressivity?
Different severity of disease with same genetic mutation
*****Note that this is different b/c here, ALL patient exhibit outward symptoms of disease
What is Marfan Syndrome?
This is a disorder of connective tissues, manifested with changes in the:
1) Skeletal
2) Ocular
3) Cardiovascular systems
What is the mutation associated with Marfan Syndrome?
- Inherited defect in Fibrillin-1 gene (FBN1)
- Located on Chromosome 15
**Note that Fibrillin-1 is also important in sequestering TGF-B, a cytokine that increases periosteal growth & has deleterious effects on vascular smooth muscle
Where is fibrillin found?
Fibrillin-1 is the glycoprotein constituent of microfibrils, a component of ELASTIC fiber in connective tissue that are especially prominent in:
1) Aorta
2) Suspensory ligament of lens
3) Periosteum
**Fibirillin is found in the elastin part of these structures
What is the specific mutation that is seen in Marfan?
Missense mutation causes glycine to replaced for cysteine leading to:
1) Progressive loss of microfibirls
2) Elastin defects
What are the symptoms of Marfan’s Syndrome? What are the three major systems that are effected in Marfan’s Syndrome?
Ocular
- Ectopia lentis
- Myopia (nearsighted)
Skeletal
- Pectus carnatum
- Pectus excavatum
- Arachnodactyly (long-slender fingers)
Cardiovascular
- Mitral valve prolapse
- Aortic bulging
- Aortic dissection
What are the major criteria for the diagnosis of Marfan’s Syndrome?
1) Pectus carinatum
2) Pectus excavatum requiring surgery
3) Lens disolcation i.e. “ectopia lentis”
4) Dissection of ascending aorta
*****Genetic findings i.e. Fibrillin-1 mutation
What is the difference between pectus excavatum & carinatum?
Pectus carinatum= “pigeon chest”
Pectus excavatum= “hollow chest”
What cytokine is most affected by Fibrillin-1 mutations?
TGF-B
What is cystic medial degeneration?
Elastic fibers, instead of running in parallel arryas are disrupted by pools of blue mucinous ground substance
What is Ectopia Lentis?
Detachment of the lens due to lax suspensory ligaments that leads to corneal flattening & near-sightedness
How does Marfan’s Syndrome affect the heart? What are the consequences?
Mitral Valve Prolapse
- Floppy/ parachute mitral valve that bulges up into the atrium
What is an aortic dissection? What are the symptoms of an aortic dissection?
Stabbing or shearing pain that radiates to the back
What is an aortic root dilation?
This is a dilation of the base of the aorta that can lead to recurgitation of the aortic leaflets into the ventricles
What is Ehlers-Danlos Syndrome?
Family of autosomal dominant disorders that primarily effect collagen leading to:
- Hypermobility
How many types of Elher’s Danlos Syndrome are there?
Six
What are Type I & II Ehler’s Danlos Syndrome?
Classic
What type of collagen is affected in Type I & II EDS?
Type V–specifically, alpha chains
What type of collagen is affected in Type IV EDS?
Type III
What collagen defects are Type V & VI EDS associated with?
Deficiency in enzymes that modify collagen, lysyl hydroxylase & lysyl oxidase
