Genetic Disorders Flashcards

1
Q

autosomal dominant

definition

A

only one good gene so heterozygotes
-will go thru all generations, both sexes
-may have delayed onset
-reduced production or inactive proteins

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2
Q

marfan syndrome gene problem

A

chromosome 15 (long arm) missense mutation in gene that encodes fibrillin-I
-no cystine for disulfide bonds, glycine instead so disordered = weak elasticity

auto dominant

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3
Q

fibrillin-I function

A

part of microfibrils aka elastic fibers in connective tissue

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4
Q

where fibrillin-I is found

A
  1. aorta (cardiovasc probs)
  2. suspensory ligament of lens (ocular probs)
  3. periosteum covering bones (skeletal)
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5
Q

fibrillin-1 mutation effects

A
  1. stiffening aortic wall
  2. inc TGF-beta1 activity
  3. inflamm, matric metallo proteases
  4. elastolysis, cell disarray
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6
Q

ocular symptoms marfan

A

displaced lens (ectopia lentis) so myopia

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7
Q

skeletal symptoms marfan

A
  1. long slender limbs (dolichostenomelia)
  2. pectus carinatum (pigeon)
  3. pectus excavatum (hollow chest)
  4. scoliosis
  5. spinder fingers (arachnodactyly)
  6. joint hypermobility
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8
Q

cardiovascular symptoms marfans

A
  1. mitral valve prolapse-mitral regurgitation
  2. dilation of ascending aorta @ root > valve incompetence > dissection/rupture
  3. cardiomyopathy- left vent enlarges as aorta widens
  4. congestive heart failure
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9
Q

criteria for marfan diagnoses

A

either 4 major features or 1 major 2 minor

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10
Q

major skeletal criterion

marfans

A
  1. pectus carinatum
  2. pectus excavatum (surgery)
  3. arm L greater than height (ULSR)
  4. wrist and thumb sign
  5. scoliosis or spondylolisthesis
  6. reduced elbow extension
  7. pes plenus
  8. protrusio acetabulae
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11
Q

other major criterion marfans

A
  1. lens dislocation
  2. dilation aortic root, dissection ascending aorta
  3. lumbosacral dural ectasia
  4. inheritance in family
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12
Q

minor criterion marfans

A
  1. pectus excavatum (no surgery)
  2. joint hypermobility
  3. high palate with dental
  4. crowding
  5. facial characteristics
  6. flat cornea
  7. mitral valve prolapse
  8. dilate pulmonary A or calcified mitral annulus below age 40
  9. recurrent or incisional hernia
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13
Q

mitral valve histology marfans

A

parachute appearance
-will close mid systole and hear click
-regurg into L atrium

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14
Q

cystic medial degeneration

marfans

A

elastic fibers are disrupted by pools of blue mucinous ground substance

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15
Q

type I and II ehlers danlos syndrome

classic

A

defective type V collagen, reduced amount

mutations in COL5A1/2 that encode alpha chain of type V
-reduced COL5A1 mRNA

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16
Q

type IV ehlers danlos syndrome

vascular

A

dec amount of type III collagen, collagen made but not exits the cell
-gene defect COL3A
-deadly

17
Q

type VII ehlers danlos syndrome

arthrochalasia VIIa,b

A

cant turn procollagen into collagen
-amino terminal procollagen peptidase deficiency so cant cleave

18
Q

EDS type I characteristics

A

-stretchy skin
-disorganized collagen, bear paw appearance

19
Q

general EDS symptoms

A
  1. hyperelasticity- stretchy skin
  2. hypermobility- unusual extension, flexion of joints
  3. skin fragility- small injuries lead to serious wounds bc wound healing faulty
  4. sutures not hold well (dehiscence)
  5. tendency to bleed (bleeding diathesis type IV)
20
Q

beighton scale for joint hypermobility

A

total score of at least 5 to dx

1 point for unilateral, 2 for bilateral
-flexion of 5th finger and thumb
-hyperextension elbow and knee
-forward flexion of trunk with knees full extended and palms on floor

21
Q

neurofibromatosis type 1

NF1

A

highly variable expression + complete penetrance
-high mutation rate, half are new mutations

22
Q

neurofibromin normal function

A

downregs function of p21 ras oncoprotein
-encodes GTPase activating protein that converts active ras-GTP to inactive ras-GDP
-aka when ras not inactivated = tumor

on chromosome 17q

23
Q

expressions of NF1

A

-cafe au lait macules
-lisch nodules
-neurofibromas
-optic gliomas
-malignancies (malignant peripheral nerve sheath tumors from plexiform neurofibromas)
-learning disabilities
-scoliosis

only 10% or less dev malignancies

24
Q

NF1 dx criteria

A

2+ present
1. 6 cafe au lait macules
2. freckling @ armpits or groin
3. 2+ neurofibromas OR 1 plexiform
4. 2+ lisch nodules @ eye
5. optic glioma
6. bone lesions (sphenoid, tibia)
7. first degree relative with NF

25
schwannoma vs neurofibroma
-schwannoma = only schwann cells, enculeate out , suppress nerve fibers -neurofibromas = mix of schwann, perineurial, fibroblasts, and mast cells, prolif within nerve fibers (resection)
26
NF2 genetics
-20% of sporadic cases are actually mosaic for mutation inactivating merlin/schwannomin tumor suppressor = NF2 associated and sporadic tumors
27
merlin function
bound to CD44 membrane signaling protein and actin -will detatch from actin and inactivate Ras
28
symptoms of NF2
1. bilateral vestibular schwannomas aka acoustic neuromas (impact CN VIII) 2. low grade CNS tumors 3. meningiomas 4. ependymomas 5. gliomas
29
criteria for definite NF2
1. bilateral vestibular schwannomas OR family history of NF2 2. plus unilateral schwannoma before 30 or any two of meningioma, glioma, schwannoma, juvenille posterior subcapsular lenticular opacities
30
criteria for probable NF2
1. unilateral vestibular schwannoma before 30 + one of (miningioma, glioma, schwannoma, juvenille lenticular opacities) 2. or 2+ meningiomas + unilateral vestibular schwannomas before 30 or one of (glioma, schwannoma, juvenille lenticular opacities)
31
presentation of symptoms NF2
hearing loss -unilateral at onset > complete deafness -VS also cause tinnitus, dizziness, imbalance
32
NF2 tumor appearance
multifocal or bunch of grapes -VS more lobular and less vascular than sporadic intracranial meningioma, spinal tumors, cutaneous tumors but more subtle than NF1 | vestibular schwannomas
33
vestibular schwannoma features
1. antoni A-dark staining, have verocay bodies (two lines of nuclei) 2. antoni B- light staining