Msk 10

Question 1

ATPase at pH 4.2 stains light for________.

Answer 1

Type 2 muscle fibers

Question 1

While the Dystrophin gene is the most related to Duchenne and Becker muscular dystrophies, what other genes are associated with the following muscular dystrophies:

Fascioscapulohumeral muscular dystrophy

Myotonic muscular dystrophy

Limb-Girdle muscular dystrophy

Answer 1

FSHD

DM1 & DM2

At least 25 subtypes

Question 1

What are the most common muscular dystrophies found in adults? And how are they characterized?

Answer 1

Myotonic Dystrophies (DM1 & DM2)

Stiffness and myotonia (sustained involuntary contraction of muscles) - may not be able to release grip

Question 2

What is the marker for muscle injury (lab)?

Answer 2

Elevated creatine kinase

Question 3

ATPase at pH 9.4 stains light for __________.

Answer 3

Type 1 muscle fibers

Question 3

Answer 3

Duchenne Muscular Dystrophy

Question 4

A patient presents with symptoms of Becker’s Muscular Dystrophy; however, the genetic deletion contains the binding site on dystrophin to dystroglycan. Is this still Becker’s?

Answer 4

No. This pt cannot anchor contractile apparatus to the sarcolemma. This is Duchenne’s Muscular Dystrophy.

Question 5

This disease occurs in both adults and children, with peaks at 10-15 and 45-60 years old.

Answer 5

Dermatomyositis

Question 6

NADH light staining is indicative of ______.

Answer 6

Type 2 muscle fibers

Question 6

DMD gene mutations are ___% new mutations and ___% deletions.

Answer 6

30% new

65% deletions

Question 6

How is polymyositis different from dermatomyositis?

Answer 6

Vascular injury isnt major

No cutaneous involvement

Limited to adults

CD8 T cytotoxic cell mediated

Blood vessels are normal with no perivascular or perifasicular infiltration

CD8 T cell infiltration - endomysial

Question 7

In a histological sample showing both degenerative and inflammatory changes characteristic of Inclusion Body Myositis, what else would be seen?

Answer 7

Inclusion bodies (vacuoles)

Cytoplasm contains intracellular protein deposits - similar to those found in Alzheimer disease

• Amyloid-ß protein
• Tau protein

Question 8

What is the genetic cause of myotonic dystrophy DM2?

Answer 8

CCTG repeat in intron 1 of ZNF9 gene

Question 9

Pt presents with:

Proximal symmetric muscle weakness

Elevated creatine kinase

Chronic perivascular and perimysial inflammatory myopathy

Perifasicular atrophy

Deposition of MAC or complement

Answer 9

Dermatomyositis - Myositis

Question 11

Adult patient presents with chest pain and facial and oropharyngeal weakness (myotonia). The physician tells his med student that death is often a result of cardiac complications in these patients. What is the diagnosis?

Answer 11

Myotonic dystrophy DM1

Question 12

DMD has the highest frequency of mutation, but does it have a higher adult prevalence than BMD?

Answer 12

No. DMD has high patient morbidity and early age of onset.

Question 13

In Myotonic Dystrophy DM2, myotonia may be minimal. What is the marked complaint of these patients?

Answer 13

Proximal muscle weakness

Also muscle pain and stiffness

Question 14

What 3 autoantibodies will yield positive tests for dermatomyositis?

Answer 14

Anti-nuclear antibody

Myositis-specific antibodies - Anti-Jo1

Dermatomyositis specific antibodies - Anti-Mi2

Question 16

NADH-TR dark staining is indicative of ______.

Answer 16

Type 1 muscle fibers

Question 18

What is the common response of myofibers to injury?

Answer 18

Necrosis

Mac’s penetrate BM

Satellite cells become myoblasts

Myoblasts fuse

Fibers are smaller & basophilic

Question 18

Does BMD result from an in-frame mutation or out-of-frame mutation?

Answer 18

In-frame

Question 20

ATPase at pH 9.4 stains dark for ___________.

Answer 20

Type 2 muscle fibers

Question 22

Denervation injury results in _______.

Answer 22

fiber grouping

Question 22

Does DMD result from an in-frame mutation or out-of-frame mutation?

Answer 22

Out-of-frame

and truncating mutations

Question 23

ATPase at pH 4.2 stains dark for \_\_\_\_\_\_.

Answer 23

Type 1 muscle fibers

Question 24

Which develops earlier in life: Duchenne's or Becker's muscular dystrophy?

Answer 24

Duchenne's - birth Becker - high prevalence due to longer lifespan

Question 25

Which inflammatory myopathy is associated with damage to small vesss in skin and muscle (C5-9 attack complex present)?

Answer 25

Dermatomyositis

Question 26

A CTG repeat in the DMPK gene causes\_\_\_\_\_.

Answer 26

Mytonic Dystrophy DM1 Indirect --\> deficiency of chloride channel CLC1

Question 27

On the DMD gene, the actin binding region is found at which terminus?

Answer 27

Amino Also 4 hinge regions Cysteine domain (CRD) Carboxy terminal domain (CTD) 24 spectrin-like repeats

Question 29

What are some genetic approaches to treat DMD?

Answer 29

Viral therapy Termination codon read-through - Ataluren Exon skipping (exon 51) - Prosensa, Sarepta Increasing Utrophin levels - similar fxn to dystrophin

Question 30

What is the function of dystrophin?

Answer 30

Links actin to the extracellular matrix Transfers force of muscle contraction to the CT

Question 31

Which form of myotonic dystrophy presents in adulthood (most common) or as congenital and child-onset forms?

Answer 31

DM1

Question 33

Which form of myotonic dystrophy is milder and presents in middle age?

Answer 33

DM2

Question 34

What is different about Inclusion Body Myositis from other idiopathic myositis syndromes?

Answer 34

Distal (not proximal) muscles are affected - knee extensors - wrist and finger flexors Disease is slowly progressive and may be asymmetric Affected individuals older than 50 CK levels only modestly elevated or normal May be a specific autoantibody - **anti-cN1A** Immunosuppressive resistant

Question 35

Pt presents with: Heliotrope rash on eyelids with periorbital edema Gottron papules on knuckles (scaly violet rash) Photo-distributed violet rash Calcinosis (calcium plaque on skin) Interface inflammation in skin - similar to SLE (associated with comlement deposition)

Answer 35

Dermatomyositis - Dermal Disease

Question 36

What treatment can be used to delay DMD by about 2 years?

Answer 36

Corticosteroids

Question 37

Cellular damage in dermatomyosities is most likely mediated by what type of immune cells?

Answer 37

B cells But both B and CD4 T helper cells are present in lesions

Question 38

Male pattern baldness Temporalis muscle wasting (hatchet face) Bilateral ptosis Perioral weakness (fish mouth) What are these features associated with?

Answer 38

Adult onset myotonic dystrophy DM1