Genetic diseases Flashcards
describe Marfan Syndrome (MFS)
- autosomal dominant disorder
- characterized by involvement of ocular, skeletal, Cardio, pulmonary and skin
- MUTATION in FIBRILLIN-1 GENE disrupts microfibrils (component of elastic fibers)
Dolichosternomelia
- unusually long and slender limbs
- sign of MFS
Pectus carinatum
pigion chest
- sign of MFS
Pectus excavatum
- hollow chest
- sign of MFS
Myopia
- present in most patients of MFS
Ectopia lentis
- displaced lens (near sightedness)
- occurs in 50% of MFS patients
arachnodactylyl
- spider fingers
- denoting the characteristically long, slender fingers
- sign of MFS
Joint hypermobility
- double jointedness
- sign of MFS
Mitral valve prolapse
- mitral regurgitation
- sign of MFS
describe the cardiovascular defects in marfan syndrome
- mitral valve prolapse
- dilation (widening) of ascending aorta leads to aortic valve incompetence may ensue and the aorta becomes susceptible to DISSECTION or rupture
- end result is congestive heart failure (How most patients die
describe Ehlers-Danlos Syndrome (EDS)
- Heterogenous group of disorders caused by mutations that alter the structure or synthesis of fibrillar collagens
- characterized by joint hypermobility, cutaneous fragility (cigarette paper) skin, hyperextensiblity
- Type I and II EDS
- Classical EDS
- characterized by mutations linked to loci that contain the COL5A1 or COL5A12 genes encoding the alpha-chains of type V collagen leading to defective type V collagen
- Type V collage = shapes and stabilizes type I collagen
type IV EDS
- Vascular - thin skin, arterial or uterine rupture, bruising are all clinical findings
- characterized by decreased amount of type III collagen
- COL3A1 mutation
- very deadly
type V and VI EDS
- are characterized by deficienceis in lysyl hydroxylase and lysyl oxidase, an important modifying enzyme in collagen biosynthesis
type VII EDS
- has amino-terminal procollagen peptidase deficiency causing it to be unable to turn procollagen into collagen
- Congenital hip dislocation
describe neurofibromatosis 1 (NF)
- Autosomal dominant disorder
- variable expressivity and 100% penetrance (if you get the disease you will have it)
- Caused by mutation of the NF-1 gene that resides on chromosome 17 and ENCODES NEUROFIBROMIN = tumor suppresor that inactivates the p21 Ras proto-oncogene (ras continues to signal and tumors develop)
what are the characteristics of NF 1
- characterized by:
- -> neurofibromas, (benign peripheral nerve tumors
- ->hyperpigmented macules (cafe au lait spots),
- -> freckling of the armpits or groin area
- ->Lisch nodules (iris pigmented melanocyte hamartomas)
describe cutaneous and subcutaneous neruofibromas in NF-1
- UNencapsulated benign tumors composed of SPINDLE CELLS = schwann cells, fibroblasts, perineurial cells
- appears as pedunculated masses and soft nodules along the course of peripheral nerves
- Plexiform neurofibromas infiltrate large nerves and cause severe disfigurement, and have potential for transformation into malignant schwannoma
Describe Neurofibromatosis Type 2
- Autosomal dominant
- Caused by a mutation in NF-2 gene on chromosome 22 that ENCODES MERLIN(also called Schwannomin) (cytoskeletal protein)
what is the characteristics of NF-2
- characterized by:
–> bilateral 8th nerve schwannomas,
–> multipe Meningiomas,
–> gliomas,
–> schwannosis ( nodular ingrowth of schwann cells into spinal cord)
–> Meningioangiomatosis (aggregates of meningothelial cells and blood vessels within the brain or brainstem)
–> cafe au lait macules, cutaneous neurofibromas, and juvenile cataracts are common
(average age of death is 36)
Compare and contrast NF-1 to NF-1
NF-1
- neurofibromin = GTPase activating protein that inactivates ras
- multiple benign neurofibromas, cafe au lait macules, iris hamartomas
NF-2
- Merlin = binds to actin and CD44
- bilateral vestibular schwannomas (acoustic neuromas) and hearing disturbances
Fibrillin-1 mutation in Marfans syndrome causes…
- stiffening of aortic wall
- increased TGF-beta activity
- inflammation
- MMP upregulation
- Elastolysis/ Cell dessarray
