Flashcards in Neurogenetics Deck (40):
1
what type of inheritance is duchenne MD
x linked recessive
2
what is the onset and progression of duchennes
delay in motor development
onset of weakness 3-4 years (pelvic and shoulder girdle)
wheelchair bound by 10-12 years
death from involvement of respiratory and cardiac muscles
3
what is the characteristic posture of duchennes
accentuated lumbar lordosis
4
what hypertrophies in duchennes
calf muscles
5
what causes duchenes
mutation in dystrophin gene in X chromosome that causes a dystrophin deficiency (dystrophin connects the contractile elements of the cell- muscle cells unable to renew and so degenerate with age)
6
what are the majority of mutations in duchennes
large scale mutations (70%)
7
how is duchennes diagnosed
gowers sign, toe walking
raised serum CK
electromyography (EMG)
muscle biopsy (not done as painful)
molecular genetic testing
8
what is autosomal recessive limb girdle muscular dystrophies
dystrophy similar to duchennes
mutation not in X chromosome so affects boys and girls equally in a recessive pattern
9
why are females protected from x linked conditions
as have other working x chromosome
10
if a mother is carrier of duchennes what is the chance of a son getting it
1 in 2
11
how many cases of duchennes are not inherited but caused by a new mutation
1/3rd
12
how prevelant is duchennes
1 in 3000
13
what mutation testing can be done in duchennes
can identify in affects or in female carriers
pre natal testing in female carriers
14
what is the screening test for duchennes
serum CPK
15
how prevelant is huntingtons disease
1 in 20,000
16
what is huntingtons disese and its symptoms
progressive neurodegenerative disorder
-onset between 30-50
-involuntary movements
-dementia
-progresses to severe dependency and death
17
what is the inheritance of huntingtons
autosomal dominant
age dependant penetrance
18
what are the early clinical signs of huntingtons
clumsiness
agitation
irritability
apathy
anxiety
disinhibition
delusions, hallucinations
abnormal eye movements
depression
19
what are the intermediate clinical signs of huntingtons
dystonia
involuntary movements
balance and gait problems
reduced manual dexterity
slow voluntary movements
difficulty initiating movements
inability to control speed and force of movement
weight loss (swallowing difficulties)
speech difficulties (dysarthric speech)
stubborness
20
what is dystonia
sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures
21
what are the late clinical signs of huntingtons
rigidity
bradykinesia (difficulty initiating and continuing movements)
severe chorea
serious weight loss
inability to walk
inability to speak
swallowing problems, danger of choking
dependence
22
what is caudate atrophy
loss of cortical tissue (caudate nuclei- usually project into the lateral ventricles)
get it in huntingtons
23
what causes huntingtons
mutations in the huntingtons gene
CAG (Codes for glutamine- in huntingtons this gene is expanded causing an accumulation of glutamine which has a neurotoxic effect)
24
why does huntingtons have earlier onset in each generation
as more repeats of the CAG gene get added each generation- neurogenerative condition
25
what does age dependent penetrance in huntingtons mean
the older you get the lower your risk of getting the condition
26
what genetic testing is done for huntingtons
pre natal and pre gestational
no known treatment to stop progession so essential to have informed consent
27
what is spinal muscular atrophy
a neurodegenerative disorder that causes progressive loss of anterior horn cells in spinal cord and brain stem nuclei
28
what is the inheritance of spinal muscular atrophy
autosomal recessive
variable age of onset and rate of progression (types 0-4 depending on age of onset)
29
what are the features of spinal muscular atrophy
proximal muscles weakness
tongue fasciculation
30
what causes spinal muscular atrophy
SMN1 deficiency (essential for survival of LMNs) due to mutation making gene unable to make mRNA
31
if both parents are carriers for spinal muscular atrophy what is the chance of the child being affected
1 in 4
32
how do drugs work against spinal muscular atrophy
mRNA which alters the pattern of slicing and allows it to retain the exon (exon 7) that would be missing in the disease- retains the proteins that would be deficient
Drug needs to be intra-thecal injected = lumbar puncture
33
what condition does alzheimer disease cause
dementia
34
who gets alzheimers
usually occurs in old age
can cause pre senile dementia
some clustering in families
35
what causes alzheimers
loss of cortical neurones
neurofibrillary tangles (intracellular proteins)
senile plaques (extracellular protein deposits)
36
what are senile plaques
extracellular protein deposits containing amyloid beta protein
37
what is the inheritance of alzheimers
autosomal dominant in 5-10% of cases (usually early onset)
common multifactoral forms
get it in down syndrome (onset in 3rd or 4th decade)
is genetically heterogenious (same phenotype produced)
38
what mutations cause autosomal dominant alzheimers
APP (amyloid precursor gene- senile plaques)
presenilin 1 and 2 (more common than APP)
ApoE (associated with familial clusters)
(APP gene involves in splicing secretase)
39
what are the types of ApoE genotypes associated with in alzheimers
E4 prediposes to the disease with clustering in families
E2 associated with longevity and old age without the disease
40