Muscular Dystrophy-TBL Flashcards
1
Q
Muscular dystrophies can be caused by mutations to genes coding for proteins in which areas?
A
sarcolemma muscle nuclei ECM muscle enzymes contractile proteins protein complexes linking the muscle to the ECM
2
Q
What is dystrophin?
A
it is a protein found on the sarcolemma that links to laminin in the ECM
3
Q
Why is it bad when the molecular glue linking the muscle to the ECM is missing?
A
b/c when the muscle contracts, it tears away from the ECM. Atrophy occurs. Leaks occur.
4
Q
Mutations to the protein dystrophin account for which 2 main conditions? What are the differences b/w these 2 mainly?
A
BMD & DMD
DMD is more severe, the complete absence of the dystrophin protein
BMD is less severe–there is still dystrophin present, but it is only partially functional & it is a truncated protein
5
Q
MDC1A affects which gene? Does it affect girls or boys more?
A
laminin-2 gene
it is autosomal–affects boys & girls equally
**it codes for a part of laminin…if this gene is mutated–don’t have the important laminin holding the ECM together
6
Q
Where is the dysferlin protein found? What conditions does a mutation in this gene cause?
A
found in the sarcolemma–attached to caveolin-3.
2 main conditions: one more severe form of the other
LGMD2B
Miyoshi Myopathy
7
Q
T/F AST & other liver enzymes have lower levels in patients with muscular dystrophy.
A
False. They have much higher levels!!
8
Q
Calf hypertrophy is found in which types of muscular dystrophy?
A
dystroglycanopathies
sarcoglycanopathies
FKRP
9
Q
Calf wasting is found in which types of muscular dystrophy?
A
LGMD2B–where dysferlin protein is messed up!!
10
Q
What characteristics do all dystroglycanopathies share?
A
all affect the dystrophin protein
X-linked recessive inheritance
11
Q
What are the 2 main types of dystroglycanopathies?
A
DMD & BMD
12
Q
Aside from DMD & BMD, what are the other forms of dystrophinopathies? These occur at lower incidence.
A
X-linked dilated cardiomyopathy Isolated quadriceps myopathy Muscle cramps with myoglobinuria Asymptomatic elevation of muscle enzymes Manifesting DMD and BMD carrier females
13
Q
T/F The dystrophin gene is relatively small.
A
FALSE! It is the largest gene!
14
Q
Where is the dystrophin gene found?
A
xp21
15
Q
How long is the dystrophin gene in the genomic DNA? How many exons make up the dystrophin gene? How large is the transcript for the dystrophin gene?
A
2.4 megabases of DNA
79 exons
14kb transcript
16
Q
Can you see a patient with DMD that doesn’t have a family history of it?
A
YES! 1/3 cases of DMD occur w/ spontaneous mutation to the dystrophin gene
17
Q
Which part of the gene is usu mutated w/ dystrophinopathies?
A
80% of cases mutation is in the center of the gene
20% of cases the mutation is near the N-terminus
18
Q
T/F More often than not, the mutation to the dystrophin gene in patients w/ DMD is near the carboxyl end.
A
FALSE! N-terminus, & when not that–center!
19
Q
What would be considered a large deletion to DNA? How many DMD patients have a large deletion?
A
large deletion: more than 1 million base pairs
66% of patients
20
Q
What percentage of DMD patients have a point mutation in their dystrophin gene? What percentage have a duplication?
A
Point mutation: 5-10%
Duplication: 5%
21
Q
T/F the course of DMD is very unpredictable.
A
False. It is very predictable, sadly.
22
Q
Why might a mom take their child into the doctor initially? If this patient is later discovered to have DMD…
A
maybe b/c the child was having a hard time holding himself up & was falling down.
23
Q
What do DMD patients usu die from?
A
pulmonary dysfunction, perhaps an infection (diaphragm muscle weak)
cardiomyopathy
24
Q
Is the CNS involved in DMD?
A
Yes.
25
What will a DMD patient's labs likely show?
high CK
| high AST & ALT
26
What would a DMD patient's MRI show?
fat & CT replacement in muscle
27
What is electrodiagnostic testing? When would it prove to be useful with DMD patients?
it tests conduction pathways
not useful when there is a family hx of DMD
may be useful in a patient with spontaneous BMD (maybe CK isn't markedly elevated & this test would help)
28
What does diagnosis of DMD require?
genetic screening for identifiable mutations of the dystrophin gene
29
In a patient w/ DMD...what would a western blot of dystrophin protein show?
A complete absence of the dystrophin protein!
30
Immunohistochemistry includes what kind of staining? What would this show for a DMD & BMD patient?
involves fluorescent antibody staining
DMD: complete absence of dystrophin on the sarcolemma (seen in cross section)
BMD: light staining (some dystrophin)
31
How is DMD inherited? Where is the mutation found? Which protein is affected? What type of muscular dystrophy is it considered? What is its incidence rate? How many of these cases are from spontaneous mutations? What is the prevalence?
X-linked recessive
Xp21
dystrophin
dystrophinopathies
Incidence Rate: 1/35,000 male live births
Spontaneous? 1/3 cases of DMD no family hx
Prevalence: 1/18K (lower than incidence b/c so many patients die at a young age)
32
How is BMD inherited? Where is the mutation found? Which protein is affected? What type of muscular dystrophy is it considered? What is its incidence rate?
```
X-linked recessive
Xp21
dystrophin
dystroglycanopathy
Incidence Rate: 1/18K-1/31K
```
33
How is MDC1A inherited? Which gene is affected? Which protein is affected?
Autosomal Recessive
6q22-23
laminin-alpha 2 chain (of laminin)
34
How does a DMD patient appear at the following ages:
Birth
Slightly after birth
2-6 years
```
Birth: normal @ birth
After birth:
meets all initial milestones with a slight delay
on close inspection, neck flexors are a little weak
2-6 years:
wide-base waddling gait
toe walker
calf hypertrophy
progressive leg weakness-->falls
Gower sign
```
35
What is the Gower sign?
when rising, a child will walk up with their hands to rise. They will put their hands on their knees & push themselves up.
36
In patients with DMD, where is their muscle weakness usu focused?
more proximally & in lower limbs (rather than upper limbs)
37
```
How does a DMD patient appear at the following ages:
8 yrs
10 yrs
12 yrs
15 yrs
Early 20s
```
```
8 years:
hard to climb stairs
10 years:
biceps, triceps, & quad reflexes are weaker or absent
12 years:
confined to a wheelchair
kyphoscoliosis
joint contractures
15 years:
definitely scoliosis spine by then
Early 20s:
respiratory function decreases
cardiac dysrhythmias increase
congestive heart failure increases
```
38
DMD
| What will you see in immunocytochemistry?
absent dystrophin
39
DMD
| Muscle biopsies--what will you see?
scattered necrotic & regenerating fibers
40
DMD
| histology of muscle--what will you see?
```
increased CT
increased inflammation
central nuclei
gaps b/w muscle fibers
fibrotic lesions
```
41
In the inflammation that is seen in DMD patients' muscle fibers...what are the cells that are present? What proportion?
cytotoxic T cells (2/3)
| macrophages (1/3)
42
If you want to look @ the quantity & size of dystrophin protein...what do you look @?
immunoblot
43
What percentage of BMD cases arise from spontaneous mutations?
10% of the cases
44
T/F DMD has a slower rate of progression than BMD.
FALSE Other way around
45
What are the clinical features of BMD?
family hx consistent w/ x-linked recessive (many men with the disease) (also seen in DMD)
ambulation past 15 yrs of age (as opposed to 12 in DMD)
Limb Girdle pattern of muscle weakness (also seen in DMD)
calf pseudohypertrophy (also seen in DMD)
cardiac abnormalities (also seen in DMD)
reduced life expectancy (less severe than DMD)
46
BMD:
| What would you see with CK levels? EMG? MRI? Histopath/Immunostaining? Immunoblot
CK levels: elevated
EMG: abnormal conduction in muscles
MRI: fatty tissue replacement of some muscle groups
Histopath/Immunostaining: less severe than DMD, dystrophin w/ N-terminal reactive antibodies but no C-terminal reactive antibodies
Immunoblot: smaller quantity & size of the dystrophin
47
Why is it that there are no C-terminal reactive antibodies for BMD?
b/c it is a truncated protein. Has the N...but doesn't get all the way to the C.
48
Which set of tests would you conduct first to test for DMD/BMD? Why?
Histopath/Muscle Biopsy
EMG/MRI
Definitely EMG/MRI b/c it is much less painful than Histopath/Muscle Biopsy (very painful).
49
Do women ever experience symptoms of DMD/BMD when they carry an affected X or no b/c it is inherited in an X-linked recessive pattern?
Sometimes, strangely enough, they actually do.
One case: If they have Turner's syndrome (1 X & it is affected).
Another Case: translocation @ the Xp21 site (in both?)
Another Case: Carriers--Lyon hypothesis--skewed x-inactivation of the normal X chromosome & dystrophin gene
50
What are the symptoms of a carrier female who seems to have DMD/BMD?
typically they are much closer to a milder form: BMD
they have limb girdle-type muscle weakness
laboratory & histologic features similar to muscular dystrophy patients
51
What are the treatment options for dystrophinopathies?
Corticosteroids
Supportive therapy: including a number of different mental & physical health specialists & maybe physical therapy & surgery
52
What type of corticosteroid is often used to treat dystrophinopathies? How long does it work for? What does it do?
Prednisone
works for up to 3 years
alters muscle metabolism (doesn't seem to work thru immunosuppression)
slows rate of deterioration
53
What are the negative side effects of long-term & high-dose use of prednisone?
```
could hurt heart function
could also cause:
weight gain
hair growth
irritability
stunted growth
hyperactivity
more susceptibility to infection
glucose intolerance
cataract formation
steroid-induced osteoporosis
osteonecrosis
```
54
Why is physical therapy especially important for DMD/BMD patients?
b/c of the contractures they experience
55
When would spinal fusion surgery be necessary for DMD/BMD patients? What would this help? What wouldn't this help?
When their scoliosis exceeds 35 degrees. This would help their comfort, but not help the resp problems associated w/ scoliosis.
56
What is contiguous gene syndrome?
this is a syndrome where a deletion is so large that it affects multiple genes. So the patient can have a super complex phenotype, including aspects of multiple diseases. This happens in some patients with DMD.
57
What is the order of the genes next to DMD that make it susceptible to contiguous gene syndrome?
Centromere-DMD-GKD-DAXI-Xpter
58
What is GKD? What are some of its symptoms?
```
glycerol kinase deficiency
severe psychomotor delay
episodic nausea
vomiting
stupor
```
59
What condition is DAXI associated with? What are the results of a deletion here?
adrenal hypoplasia congenita
| lifethreatening adrenal insufficiency
60
What is Emery-Driefuss Muscular Dystrophy (EDMD)?
a condition caused by a mutation to the gene encoding the emerin protein.
61
What is the fcn of the emerin protein?
nuclear scaffolding protein in the inner nuclear membrane (attaches heterchromatin)
62
What is the inheritance pattern of EDMD? What are its results?
X-linked recessive
weakness & wasting in upper arms, shoulders, legs
heart problems--ventricular myocardial disease & sometimes conduction block leading to sudden death
63
What would the CK be like in a patient w/ EDMD? How can you diagnose & confirm the diagnosis for this condition?
CK elevated
diagnose w/ skin biopsy
can confirm the diagnosis w/ DNA testing
64
What's the deal with female carriers of the X chromosome w/ a mutation to the emerin gene?
they should get regular ECGs b/c in later life they could develop heart problems & die suddenly.
65
What is the heterogenous group of disorders called that resemble dystroglycanopathies except that they are inherited in an autosomal fashion?
LGMD: limb girdle muscular dystrophy
66
What is the prevalence of LGMD? What is the inheritance pattern? Do they all have the same clinical, lab, & histo features?
8-70/10^6
inherited in the autosomal recessive (LGMD2) or autosomal dominant (LGMD1) manner.
No...different features w/i the heterogeneous group.
67
What is the mutation that causes LGMD1A? What is the inheritance pattern? What protein does it mess with? Are spontaneous mutations common? What are the labs like?
```
mutation @ 5q22.3-31.3
autosomal dominant
messes w/ myotilin
spontaneous mutations ARE common
elevated CK in labs
```
68
What is myotilin's fcn?
sarcomeric protein
| it is found @ the Z disc & is w/ alpha actinin
69
What would a muscle biopsy of a patient w/ LGMD1A show?
Rimmed vacuoles
| nemaline rod-like inclusions
70
What are the clinical features of LGMD1A?
progressive weakness--could begin early or late in life
distal leg & some arm weakness
cardiomyopathy
71
What is the mutation that causes LGMD1B? What is the inheritance pattern? What protein does it mess with? Are spontaneous mutations common? What are the labs like?
```
mutation @ 1q11-21
autosomal dominant
messes w/ lamin A/C
spontaneous mutations not mentioned to be common
elevated CK
```
72
What is the function of lamin A/C?
vital for nuclear cytoskeleton organization
73
What would histo show in a patient w/ LGMD1B?
myofiber size variation
CT depositioin
loss of peripheral heterochromatin by myonuclei
74
What are the clinical features of LGMD1B?
weakness in hip & shoulder girdle
| cardiac conduction abnormalities (require a pacemaker to prevent sudden death)
75
What is the mutation that causes LGMD1C? What is the inheritance pattern? What protein does it mess with? Are spontaneous mutations common? What are the labs like?
```
mutation @ 3p25
autosomal dominant
messes w/ caveolin-3
spontaneous mutations ARE common
elevated CK
```
76
What is the function of caveolin-3?
it is found on the sarcolemma & it is involved in cell signaling & sodium channels
important for the formation of caveoli (invaginations of the sarcolemma) & important for muscle contraction
77
What would the histo of a patient w/ LGMD1C show?
myopathic changes
| decreased caveoli
78
What is the best way to diagnose LGMD1C?
Western Blot: shows complete absence of caveolin-3
| immunofluorescence is ok, just not as good.
79
What are the clinical features of LGMD1C?
heterogenous phenotype (everyone is different!)
in childhood or adulthood proximal weakness & exertional myalgia
calf hypertrophy
rippling muscle disease
distal weakness
80
What mutation causes LGMD2A? What is the inheritance pattern? What group of disorders does it belong to? What protein does it mess with? What are its lab features?
```
mutation @ the calpain-3 gene
messes w/ calpain
autosomal recessive
calpainopathies
CK normal or high
MRI shows fat & CT replacement
```
81
What does the histopath of LGMD2A show?
myofiber size variation
| endomysial CT
82
What are the clinical features of LGMD2A?
changes pelvic girdle muscles & posterior thigh muscles
w/i 5 yrs (scapula wings) & humoral muscle weakness
contractures & elbows & calves
non-ambulatory by age 20
normal life expectancy
83
What is the screening for LGMD2A? What is the confirming test?
screening: Western Blot
Confirmation: CAPN3 sequencing
84
What mutation causes LGMD2B/MM? What is the inheritance pattern? What protein does it mess with? What class of disorders is it included in? Labs?
```
mutation @ 2p13
messes w/ dysferlin protein
dysferlinopathies
autosomal recessive
elevated CK
```
85
Dysferlinopathies account for 60% of _________.
distal myopathies
86
When do you start seeing symptoms of LGMD2B/MM & what is its progression like?
start seeing symptoms in adulthood & it has a slow progression
87
What is the histopath like for someone with LGMD2B/MM?
dystrophic muscle features
| endomysial or perivascular inflammatory process
88
What is LGMD2B/MM sometimes incorrectly diagnosed as?
polymyositis
89
What are the clinical features of LGMD2B/MM?
some people lose ambulation by their 20s & others are able to walk late in life
90
What is the difference b/w LGMD2B & Miyoshi Myopathy (MM)?
LGMD2B: more severe, proximal lower girdle muscles affected
MM: only calf muscles affected
91
What is the usual method of checking for LGMD2B or MM? What is the method for confirming?
checking: immunofluorescence
confirming: sequencing
92
We are now generally talking about LGMD2.
| Which disorders in this family DON'T show calf hypertrophy?
LGMD2B
| dysferinopathies!
93
Which of the LGMD2 disorders is cardiac involvement rare in? Which ones is it common in?
Rare in: calpain & dysferlin deficiency
| Common in: sarcoglycan & FKRP
94
Which of the LGMD2 disorders do you see a DMD-like phenotype in?
sarcoglycan
calpain
FKRP
95
What is merosin?
alpha 2 chain of laminin
96
What mutation causes MDC1A? Which protein is affected? What do the labs show?
on chromosome 6
LAMA 2-gene
see absence of merosin (laminin211 & 221)
Elevated CK
97
Laminin is critical for ____ _____.
muscle regeneration.
98
What is the histopath like for MDC1A patients?
small muscle fibers
inflammatory cells
myofiber loss
fibrosis
99
What would a CT of a patient w/ MDC1A show?
lucencies of white matter
100
What would an MRI of a patient w/ MDC1A show?
increased signal on white matter on T2-weighted images
see more white matter esp in forebrain (increased risk for seizures) b/c of the laminin alpha 2 deficiency (critical for myelination)
101
Describe what brain stuff happens to patients w/ MDC1A.
in teen years: a lot of seizures
| but normal intelligence
102
Aside from the ones already listed, what are some other symptoms of MDC1A?
contractures, esp in hips & feet
floppy baby syndrome
severe weakness of the trunk & limbs & hypotonia @ birth
103
Which disorders are included under the classification of sarcoglycanopathies?
LGMD2C-LGMD2F
104
Sarcoglycanopathies (2c-2F) consist of a mutation affecting what protein complex? Where is the complex found? What is it connected to?
sarcoglycan complex
found in the sarcolemma
connected to the dystroglycan complex
105
What part of the world has a lot of sarcoglycanopathies?
North Africa
106
How many sarcoglycan genes can be affected? Which proteins are affected?
4 sarcoglycan genes: affecting gamma, alpha, beta, or delta proteins in the sarcoglycan complex.
107
What are the common clinical features of sarcoglycanopathies?
```
their onset is b/w 10yr & 30yrs of age.
Loss of ambulation happens b/w 20yr & 40yr.
Some heart problems can be present
limb girdle weakness
particularly trunk & limb weakness
calf hypertrophy
sometimes Gower's sign is present
```
108
How are all sarcoglycanopathies inherited? What would labs show for a patient w/ a sarcoglycanopathy?
autosomal recessive
| elevated CK
109
LGMD2C is associated w/ which protein specifically? What is its distinguishing feature?
gamma protein
| mimics symptoms of DMD
110
LGMD2D is the most common sarcoglycanopathy. Which protein is it associated with specifically? What is its distinguishing feature?
alpha protein
| has both a severe & mild form
111
LGMD2E is associated w/ which protein specifically? LGMD2F?
LGMD2E: beta protein
LGMD2F: delta protein
112
LGMD2I is also called what? How is it inherited? What part of the world is it common in? What are its labs like?
FKRP
aut recessive
UK & Germany
elevated CK in labs
113
What are the clinical features of LGMD2I?
heart involvement common
Like DMD but more mild: calf hypertrophy, resp failure
Facial weakness
Tongue & leg hypertrophy
Overall: variable in onset & presentation
114
Congenital MD disorders have what common features?
hypotonia
weakness
onset: birth-6 months
high CK
115
What is merosin?
alpha 2 chain of laminin
116
Which congenital MD disorders have a major brain abnormality?
Fukuyama
Muscle Eye Brain Disease
Walker Warburg Syndrome
117
Selenoprotein N disorders consist of which 2 conditions? How are they inherited? They have the same clinical features, but they have different histo features. What are the histo differences?
Autosomal Recessive
MMCD: Multi Mini Core Disease (congenital myopathy)
Histo: mini cores seen
Rigid Spine Syndrome (congenital muscular dystrophy)
Histo: no mini cores seen
118
Collagen 6 MD consists of which 2 disorders? What are the main clinical features of Collagen 6 MD? What is a histo feature?
```
Bethlem Myopathy
Ullrich Congenital MD
Clinical Features:
hyperelasticity
rought texture to skin
contractures
Histo: fuzzy matrix
```
119
With Bethlem Myopathy, is it mild or severe? Rec or Dom? When is its onset? What does it consist of?
Mild
Dominant Inheritance
Onset @ childhood
Muscle Wasting
120
With Ullrich Congenital MD, is it mild or severe? Rec or Dom? When is its onset? What does it consist of?
```
Severe
Recessive Inheritance
Onset @ Birth
Distal Laxity
Resp muscles affected
Abnormal scarring
```
121
What are dystroglycanopathies?
they are disorders caused by lack of proper glycosylation of alpha dystroglycan in the dystroglycan complex.
This protein is glycosylated as it goes thru the ER & Golgi. If there are messed up enzymes here: dystroglycanopathy. These have major brain effects.
122
Why does the alpha dystroglycan even need to be glycosylated?
b/c it needs to be able to stick to laminin!
123
T/F The later the glycosylation mutation in the glycosylation pathway for alpha dystroglycan, the more mild the defect.
False!! The earlier...the worse! POMT1 & 2 in the ER are the earliest & the worst.
124
What is the order of glycosylation of alpha dystroglycan thru the ER & Golgi?
```
ER: POMT1 & POMT2
Golgi:
POMGnT1
Fukutin
FKRP
LARGE
LARGE2
```
125
In Walker Warburg Syndrome, what is the messed up protein? Is it mild or severe? When does it begin? What are its characteristics?
POMT1 messed up, the glycosylator of alpha dystroglycan in the ER.
Severe.
Begins in utero.
encephaloceles present
type II lissencephaly (smooth brain-no grooves)
126
Which 3 disorders w/i congenital muscular dystrophies constitute major brain abnormalities?
Fukuyama
Muscle Eye Brain Disease
Walker Warburg Syndrome
127
Which protein is messed up in Muscle Eye Brain Disease? How is it inherited? What does the MRI show?
POMGnT1 in the Golgi is messed up.
Autosomal Recessive
MRI shows brain abnormalities
128
What are the symptoms of Muscle Eye Brain Disease? If you have this, what other deficiencies should you watch out for?
```
Muscle: hypotonia
Eye: myopia, glaucoma
Brain: intellectual & brain problems
Watch out for:
merosin deficiency
alpha dystroglycan deficiency
```
129
MDC1C is caused by a mutation to which protein? What is its sister disease? What are the labs like?
FKRP (in the Golgi)
Sister Disease: LGMD2I
Labs: high CK
130
What are the symptoms of MDC1C & LGMD2I? Is MDC1C severe or mild?
leg hypertrophy
big tongue (macroglossia)
dilated cardiomyopathy
SEVERE
131
Which protein is messed up in Fukuyama (FCMD)? How is it inherited? Which country is it found in?
Fukutin (Golgi-glycosylation)
Autosomal Recessive
Japan-founder thing
132
What is the prognosis for Fukuyama?
will probably die by 16 years of age.
133
Where is the mutation for Fukuyama?
9q31-33
134
What do the labs show for Fukuyama? What does the MRI show?
Labs: elevated CK
MRI: brain problems
135
What does the histopath show for Fukuyama?
fibrosis
inflammation
myofiber loss
136
What are the main clinical features of Fukuyama?
floppy baby syndrome, otherwise normal @ birth
contractures
mental retardation
skull asymmetry
137
If you have Fukuyama, what do you worry about secondarily?
deficiency in laminin-alpha 2
| deficiency in alpha dystroglycan
138
In Myotonic Dystrophy Type I (DM1) which protein is messed up? Where is the gene mutation located? What is the nature of the mutation? What interesting genetics inheritance thing does this disease show?
DMPK (a kinase)
19q13.3
CTG repeat expansion
Inherited Autosomal Dominant-shows anticipation (gets worse w/ each generation)
139
What is the incidence of DM1? When does it begin usually? What are its symptoms?
```
1/8K
Begins in teen years
Distal Muscle Weakness
Progressive Muscle Wasting
Footdrop
Long face that looks mournful
heart problems
```
140
Myotonic Dystrophy Type II (DM2) is also called what? How is it inherited? Does it show anticipation? Is it more mild or more severe than DM1?
PROMM
Autosomal Dominant
No anticipation
More mild than DM1
141
What do the labs show about DM2?
CK high
insulin insensitivity in some patients
Low testosterone
142
What is the mutation issue w/ DM2/PROMM?
CCTG expansion in intron 1 of ZNF9
143
What is ZNF9?
a zinc finger protein
144
When is the onset usu of DM2/PROMM? What do you first notice? What might you eventually experience?
Ages 20-60
Pain & stiffness in thighs @ first
Eventually possible to have: weakness in proximal, distal & facial muscles
145
Facioscapulohumeral Dystrophy (FSHD) is inherited how? What cool genetic thing does it show? What is its prevalence? Why is its prevalence so high?
FSHD is inherited in an autosomal dominant manner & shows anticipation (gets worse w/ each generation).
Prevalence: 1/50K-1/100K
High prevalence b/c these patients live, not necessarily a high incidence.
146
What would labs for FSHD patients show? Is DNA testing available for this condition?
shows high CK
| DNA testing IS available!
147
FSHD1 & FSHD2 are very similar, but there are different mutations that lead to them.
What is the mutation that causes FSHD1?
deletion in D4Z4 region of 4q35. Therefore, fewer introns & DUX4 gene is turned on. This is a killer gene. Bad for body.
148
What is the mutation that causes FSHD2?
hypomethylation in D4Z4. Should be heterochromatin & non-expressed. In this case, DUX4 gene is expressed & is bad for the body-killer gene. But people live long lives.
149
Is FSHD2 common?
No. 5% of cases. Most of these patients have FSHD1.
150
What is the clinical presentation of FSHD?
skeletal muscle weakness in the face, scapula, & arms.
Shoulder weakness, hard to put things above your head.
Footdrop.
Asymmetric weakness, though. Not everything affected evenly.
