Muscle Flashcards
1
Q
Biopsy finding in Nemaline myopathy?
A
Rods
2
Q
Biopsy finding in Central core disease?
A
Cores
3
Q
Biopsy finding in myotubular myopathy?
A
Central nuclei
myotubular/centronuclear myopathy
4
Q
Which myopathy can present with malignant hyperthermia?
A
Central Core Disease
RYR1 gene
Tx: Dantrolene
5
Q
What is the most common type of congenital muscular dystrophy?
Mutation?
A
Merosin-deficient CMD LAMA2 mutation (laminin-a2)
6
Q
What are the mutations for
DMD
BMD
A
DMD:
Dystrophin gene, Xp21
Altered frame mutation
BMD:
Dystrophin gene, Xp21
In-frame mutation
7
Q
Re FSHD:
Mode of inheritance Age at presentation Genetic abnormality Neurologic presentation Systemic clinical presentation
A
AD
2nd decade
Contraction mutation, D4Z4
DUX4 retrogene
Asymmetric weakness of F,S muscles
Hearing loss,
Retinal telangiectasias, exudates, detachment (Coats disease)
Atrial arrhythmias
8
Q
For Oculopharyngeal Muscular Dystrophy
A) Genetic abnormality
B) Clinical presentation
A
A) PABPN1, AD
B) Age: 50s; Ptosis, dysphagia, ophthalmoparesis (late)
9
Q
Emery-Dreifuss Muscular Dystrophy
A) Clinical presentation?
B) Genetic abnormality?
A
EMD-1: Contractures -> weakness
EMD-2: Weakness -> contractures
Systemic: conduction abnormalities, CM
EMD-1: STA gene (emerin), X linked
EMD-2: LMNA (lamins A and C), AD/AR
10
Q
What are the modes of inheritance and general characteristics of:
LGMD-1
LGMD-2
A
LGMD-1: AD, normal CK*
LGMD-2: AR, high CK, more common
*except LGMD1C (high CK, rippling muscles)
11
Q
What are the genetic abnormalities and key features of the following
LGMD1A
LGMD1B
LGMD1C
LGMD1E
A
LGMD1A - MYOT, dysarthria
LGMD1B - LMNA, contractures
LGMD1C - CAV3, rippling, inc CK
LGMD1E - Unknown, myofibrillar myopathy, cardiomyopathy
12
Q
What is the most common LGMD?
Genetic mutation?
Presentation?
A
LGMD2A (calpainopathy)
CAPN3 mutation
Proximal lower extremity > upper Ex weakness
Scapular winging
13
Q
What are the genetic abnormalities and/or key features of the following
LGMD2B
LGMD2I
LGMD2C-F
A
LGMD2B - DYSF (dysferlinopathy), a/w Miyoshi myopathy (calf wk)
LGMD2I - FKRP, dystroglycanopathy
LGMD2C-F - Sarcoglycanopathies
14
Q
Mutations in which gene causes IBM + Paget disease + FTD?
A
VCP
15
Q
Carnitine Palmitoyltransferase Deficiency II:
A) PP
B) Clinical presentation
C) Triggers of rhabdo
A
A) Transport of ACYLCARNITINE across inner mitochondrial membrane impaired
B) 1st-2nd decade: Paroxysmal myoglobinuria on prolonged exercise, myalgia
C) Meds: diaz, VA, anesthesia
Fs: fasting, fever, fat intake, fection
16
Q
McArdle Disease / Glycogenosis Type V
A) PP/Genetics
B) Clinical presentation
C) Diagnostics
D) Treatment
A
A) PYGM gene, myophosphorylase defiicency
B) SECOND WIND phenomenon
Triggered by BRIEF exertion w/ ISOMETRIC contractions,
Exercise intolerance, contractures
C) Forearm ischemic exercise test: no increase in lactate
Bx: subsarcolemmal glycogen deposits
D) High protein, low-carb; sugars before exercise
17
Q
Pompe Disease / Glycogen Storage Disease Type II
A) PP/Genetics
B) Clinical presentation
C) Diagnostics
D) Treatment
A
A) A-1,4 glucosidase (GAA) / Acid Maltase deficiency
B) Infantile - hypotonia, macroglossia, hepatomeg, cardiomeg, death
Juvenile (1st decade), Adult (3rd-4th d): proximal muscle weakness, respiratory muscle weakness
C) Vacuoles w/ glycogen and overreactive for acid phosphatase
D) Enzyme replacement therapy
18
Q
Classify the following:
Pompe Disease
McArdle Disease
CPTII
A
Pompe Disease - Glycogen storage (type II)
McArdle Disease - Glycogenosis (type V)
CPTII - lipid metabolism disorder
19
Q
Myotonic Muscular Dystrophies:
What are the two types?
A
DM1 - Steinert Disease
DM2 - Proximal myotonic myopathy
20
Q
Myotonic Muscular Dystrophies:
What are the genetic abnormalities?
A
DM 1 (Steinert) - DMPK, CTG rpts
DM2 (Proximal myotonic myopathy) - ZNF9, CCTG rpts
21
Q
Myotonic Muscular Dystrophies:
Myopathic features?
Systemic features?
Biopsy features? (type 1 vs type 2)
A
Myopathic:
1 - DISTAL wk, myotonia of hands, facial weakness, ptosis, temporal muscle wasting,
Adams: hatchet face, swan neck, foot drop
2- PROXIMAL wk, calf hypertrophy
Systemic:
FECCCCC (MC in DM1)
Frontal baldness Endocrinopathies Cataracts (posterior subcapsular) Cardiac conduction defects, CM Central sleep apnea Cognitive dysfunction
Biopsy:
DM1 - type 1 fibers
DM2 - type 2 fibers
22
Q
Myotonic Muscular Dystrophies:
Treatment?
A
Mexiletine
23
Q
Myotonia Congenita
2 types?
Inheritance?
W/c is more common?
A
Thomsen myotonia - AD
Becker myotonia - AR, more common
24
Q
Genetic abnormality in Myotonia Congenita?
Paramyotonia Congenita?
A
Myotonia Congenita
CLCN1
Paramyotonia Congenita
SCN4A
25
Onset < 20 y
Progressive external ophthalmoplegia
Proximal muscle weakness
A/F: retinitis pigmentosa, conduction defects, short stature, hearing loss, dementia, ataxia, endocrine d/o
Kearns-Sayre Syndrome
| Single large mDNA mutation
26
Progressive external ophthalmoplegia
Sideroblastic anemia
Pancreatic dysfunction
Pearson Syndrome
27
Which inflammatory myopathy is associated with interstitial lung disease? What are the antibodies implicated?
Dermatomyositis
| Anti-Jo 1 antibodies
antisynthetase syndrome
28
Which inflammatory myopathy is associated with autoimmune diseases such as Sjogren, SLE, Raynaud?
Dermatomyositis
29
What are the muscle biopsy findings for
Dermatomyositis
Inclusion body myositis
Polymyositis
DM - Perifascicular atrophy, perimysial inflammatory reaction
IBM - red-rimmed vacuoles on GTS
PM - CD8 lymphocytes, endomysial inflammatory reaction
30
W/c inflammatory myopathy presents w/ EMG: mixed myopathic + neurogenic findings?
IBM
31
W/c inflammatory myopathy is most a/w CA?
Dermatomyositis
32
Which medication can cause a mitochondrial myopathy a/w ragged red fibers?
Zidovudine (AZT)
33
Statin-induced myositis is a/w reduced levels of ____
Genetic abnormality?
CoQ10
SLCO1B1 gene
34
Which LGMD affects titin?
LGMD 2J
35
This part of the sarcomere is responsible for stabilization and length determination of thin filaments. It spans the entire structure of thin filaments
Nebulin
36
Maintains structural integrity of sarcomere during both active and relaxed states
Titin
37
Where is the M line located?
Center of the A band
38
Where are titin filaments located?
Z disk - M line
39
Area of overlap of actin and myosin filaments
A band
40
Area that includes only thin filaments
I band
41
Mechanical attachment between adjacent sarcomeres
Z disk
42
Region containing only myosin filaments
H zone
43
Genetic abnormality in Nemaline Rod Myopathy
Nebulin (NEM2)
a-Tropomyosin
Coflin-2
B-Tropomyosin
Ryanodine Receptor
Troponin T1
a-actin
44
Congenital myopathy presenting as facial weakness, high-arched palate, and high pedal arches
Nemaline Rod Myopathy
45
Myotubular Myopathy
MC genetic abnormality and pattern of inheritance?
Common time of onset?
MTM1 gene, X-linked
| In utero onset
Myotubularin impt for differentiation in late myogenesis
46
This disease can present with congenital absence of a muscle (amyoplasia of one pectoral, brachioradialis, or biceps femoris)
Facioscapulohumeral Muscular Dystrophy (DUX4 mutation)
47
First manifestations are difficulty raising the arms above the head and winging of the scapulae
Deltoids remain large and strong
Angel-wing appearance - scapulae are winged and elevated
Popeye effect - upper arm may be thinner than the forearm
FSHD
48
A group of muscles, after a series of strong contractions, remain shortened for many mins bec of failure of metabolic mechanism necessary for relaxation.
True physiologic contracture
49
Muscle and tendon shortening following prolonged fixation and inactivity of the normally innervated muscle (ex. Broken limb immobilized).
Pseudocontracture / Myostatic or Fibrous contracture
50
Another form of fibrous contracture found in newborns.
Arthrogryposis
51
Condition where there are repeated twitching and rippling of a muscle at rest
Myokimia
52
Infectious myopathy presenting with weakness of the EOMs, tongue, masseter, pharyngeal muscles, proximal limb muscles, diaphragm, myocardium
“Puffy face + tender muscles”
Trichinosis
53
Which infectious myopathy can present with “dramatic pseudohypertrophy of thigh and calf muscles”?
Cysticercosis
54
Which of the following is TRUE regarding HIV myositis?
A) Painful weakness of the girdle and proximal limb muscles
B) Reflexes are not affected
C) EMG shows active myopathy (fibrillations, brief polyphasic motor units, complex repetitive discharges)
D) Presence of nemaline (rod) bodies within type 2 fibers
E) No medications are known to be effective. PT and supportive care are the cornerstones.
True: C) EMG shows active myopathy (fibrillations, brief polyphasic motor units, complex repetitive discharges)
* PAINLESS weakness of the girdle and proximal limb muscles
* Reflexes are DIMINISHED
* Presence of nemaline (rod) bodies within type ONE fibers
* CORTICOSTEROIDS are effective in ameliorating the weakness
55
Which of the following is NOT known to cause sporadic myositis w/ rhabdomyolysis?
```
A) Echo 9
B) Dengue
C) Adenovirus 21
D) Herpes simplex
E) EBV
F) Coxsackievirus
G) M. Pneumoniae
```
B) Dengue
56
Which of the following is TRUE regarding Dermatomyositis?
A) More common in older people aged 50 and above, more commonly males
B) Gottron papules are found over the flexor surfaces of the joints
C) Usual mode of onset is painful weakness of proximal limb muscles (hips, thighs)
D) Ocular muscles are involved
E) Distal muscles (forearm, hand, leg, and foot) are spared in 75% of cases
True: E) Distal muscles (forearm, hand, leg, and foot) are spared in 75% of cases
* DM affects children = adults. Adults: Women > Men, Children: Women = Men. Age 30-60. Peak incidence15 years “in a smaller group”
* Gottron papules are found over the EXTENSOR surfaces of the joints
* Usual mode of onset is PAINLESS weakness of proximal limb muscles (hips, thighs)
* Ocular muscles are NOT AFFECTED
57
Carcinoma is associated with which inflammatory myopathies?
Dermatomyositis > Polymyositis
58
Which neoplastic processes are linked most often with myositis?
A) In men
B) In women
Men: lung, colon CA
Women: breast, ovarian CA
59
Which of the following is not part of the synthetase syndromes (associated with DM)?
```
A) Interstitial lung disease
B) Arthritis
C) Uveitis
D) Raynaud syndrome
E) Mechanic’s hands
```
C) Uveitis
60
True or false. Serum CK levels tend to be higher in DM than PM
False. CK levels are higher in PM than DM.
61
In necrotizing inflammatory myositis, a proportion of patients display antibodies to ______, the target of statin drugs.
HMGCR
62
Location of inflammatory infiltrates in
DM
PM
Dermatomyositis: PERImysium
Polymyositis: ENDOmysium
63
In which inflammatory myositis can you find microvascular changes in muscle?
Dermatomyositis
64
In which inflammatory myopathy can you find immune complexes, IgG, IgM, C3, and MACs deposited in the walls of venules and arterioles?
Dermatomyositis
65
In which inflammatory myopathy can you see activated T cells (CD8) and sparse B cells?
Polymyositis
66
Differentiate types of immune responses responsible for DM and PM
DM: Humoral
PM: Cytotoxic
67
Which of the following is TRUE regarding Inclusion Body Myositis?
A) Most common in pts older than 50 years, Females > Males (3:1)
B) Associated with diabetes, autoimmune diseases, and polyneuropathy
C) Selective weakness of the deltoids, sparing of the thumb flexors
D) Knee jerks are depressed once quadriceps atrophy becomes severe
E) CK is greatly elevated
True: B) Associated with diabetes, autoimmune diseases, and polyneuropathy
* Most common in pts older than 50 years, MALES > females (3:1)
* Selective weakness of the THUMB FLEXORS, sparing of the DELTOIDS
* Knee jerks are depressed EVEN WITHOUT quadriceps atrophy
* CK is normal or SLIGHTLY elevated
68
IBM diagnostics:
EMG findings?
Histopathologic findings?
Cytosolic antibodies implicated?
EMG findings?
Myopathic (like PM) + Neuropathic (due to chronicity)
Histopathologic findings?
Rimmed vacuoles. Intracytoplasmic, subsarcolemmal vacuoles, eosinophilic inclusions in cytoplasm and nuclei of degenerating muscle fibers.
Cytosolic antibodies implicated?
Anti-cN1, NT5C1A
69
When is DMD usually recognized? (Adams)
3rd year of life
| Always before the 6th year
70
Which of the following is NOT true of DMD?
A) Foot-drop and toe-walking are due to weakness of the iliopsoas, quadriceps, and gluteal muscles w/c are involved first
B) The waddle is the result of bilateral weakness of the gluteus medius
C) Oral, facial, bulbar, and hand muscles are involved later on in the disease
D) The habitual posture for DMD is lumbar lordosis, hip flexion and abduction, knee flexion, and plantar flexion
E) Death is usually the result of pulmonary infections
F) Average IQ is 85
C) Oral, facial, bulbar, and hand muscles are involved later on in the disease
* these are usually spared
71
What is the largest gene known to humans?
Dystrophin gene
72
What is the consequence of dystrophin pathology?
Renders sarcolemma susceptible to breaks and tears during contraction.
73
What are the genetic abnormalities implicated in Emery-Dreifuss Muscular Dystrophy?
A) X-linked (MC)
B) AD
C) X-linked
A) X-linked: EMD (emerin)
B) AD: Laminin A/C
C) X: linked: FHL-1
74
What is the distinguishing feature of the most typical form of Emery-Dreifuss MD?
Early appearance of contractures in the flexors of the elbow, extensors of the neck, and posterior calf muscles.
75
Most common form of limb-girdle dystrophy in patients of Northern European descent.
LGMD 2I (FKRP, Fukutin Mutation)
76
What is the mutation in LGMD2I?
FKRP, Fukutin mutation
77
True or false. IN LGMD2I, a period of stabilization lasting several to 35 years is common, followed by a decade or more of progression that eventually involves the shoulder muscles.
True.
78
Which LGMDs are considered sarcoglycanopathies?
LGMD 2 C, D, E, and F
79
This accounts for 40% of pts with LGMD
The abnormal gene codes for which protease?
What is the clinical presentation that permits distinction from the sarcoglycanopathies?
LGMD2A
Calpain
Achilles tendon contractures, very high CK levels
80
What is the abnormality in LGMD2B?
This is also involved in the distal form of which muscular dystrophy?
What are clinical clues that can point towards this disease?
Dysferlin (muscle fiber membrane)
Distal form of Miyoshi muscular dystrophy
Early involvement of the gastrocnemius (inability to tiptoe)
81
What is the protein abnormality in LGMD 1A?
Main clinical characteristics?
Allelic to a form of?
Myotilin
Proximal leg weakness, elevated CK
Myofibrillar myopathy
82
LGMD 1B is caused by mutations in the gene encoding which nuclear membrane protein?
Lamin A/C
83
Age at onset of Oculopharyngeal Dystrophy (PABPN1 mutation)
After the 45th year
84
For Miyoshi Dystrophy:
Mutation?
Onset?
Presentation?
Association?
DYSF (dysferlin)
*dysferlin - Ca-mediated membrane repair
Onset - early adult life
Presentation - weakness, atrophy of leg muscles - distal (peronea, gastroc, soleus)
LGMD2B
85
Gene/protein abnormality for Merosin deficiency
LAMA2/Merosin
86
True or false. In Merosin deficiency, cognitive function is affected.
False
87
Seizures are common in the following EXCEPT:
A) Merosin deficiency
B) Fukutin CMD
C) Muscle-eye brain disease
D) Walker-Warburg disease
A) Merosin deficiency
88
Gene/protein abnormality for Rigid spine syndrome
SEPN1/Selenoprotein
89
Gene/protein abnormality for Muscle-eye brain disease
POMGnT1I / N-acetyl-glucosaminyl-transferase
90
Gene/protein abnormality for Walker-Warburg disease
POMT1 / O-Mannosyl-transferase 1
91
What has been found to increase muscle mass in patients with myotonic dystrophy?
Testosterone
92
Pattern of inheritance for the glycogenoses?
Autosomal Recessive
93
True or false. Patients with Pompe disease are suscptible to general anesthesia
True
94
What is the most common form of Pompe disease?
A) Infantile form
B) Juvenile form
C) Adult form
A) Infantile form
95
Which glycogen storage myopathy can present with pseudomyotonia on EMG?
Pompe Disease
96
What is Tarui Disease?
Phosphofructokinase deficiency
| Ashkenazi Jewish men
97
Name the Glycogenosis:
Hepatomegaly, myopathy
Hallmark: basophilic PAS (+) polysaccharide granules in skin and muscle
Type IV glycogenosis
Andersen disease
Branching enzyme deficiency
98
Glycogenosis that is inherited as a sex-linked recessive trait.
Hemolytic anemia, mental retardation, seizures, tremor.
Type IX glycogenosis
Phosphoglycerate kinase deficiency
PGK1 mutation
99
Where are CPT I and II found?
CPTI - outer mitochondrial membrane
CPTII - inner mitochondrial membrane
100
What is the mutation in Carnitine Palmitoyltransferase Deficiency?
CPT1A mutation
101
Which is the most common type of Carnitine Palmitoyltransferase Deficiency?
A) Type I
B) Type IIA
C) Type IIB
A) Type I
102
Which of the following is TRUE regarding Thyrotoxic Hypokalemic Periodic Paralysis?
A) Causes weakness of the muscles of the trunk and limbs, cranial muscles are involved
B) 1/2 have had hyperthyroidism, common in Asian males
C) Familial disorder
D) Mutation in KCNA1a
True: B) 1/2 have had hyperthyroidism, common in Asian males
* Causes weakness of the muscles of the trunk and limbs, cranial muscles are NOT involved
* NOT a familial disorder
* Mutation in Kir2.6
103
Which of the following is NOT prominent in Hypothyroid Myopathy?
A) Myospasm, Myokimia
B) Slowness of contraction and relaxation phases of tendon reflexes
C) Percussion myoedema
D) Weakness
D) Weakness
104
What kind of steroids are more likely to cause myopathy?
Fluorinated
105
The use of this medication is a factor in > 80% of critical illness myopathy cases
Neuromuscular blocking agents
106
What is the identifying histologic feature in Critical Illness Myopathy?
Striking loss of thick (myosin) filaments
107
What is the most important myopathic abnormality in hypo and pseudohypoparathyroidism?
Tetany (low iCal)
108
Variants in this gene that codes for an organic anion-transporting polypeptide confers a risk of statin myopathy.
SLCO1B1
109
Which of the following is TRUE of Colchicine myopathy?
A) Muscle biopsy shows elements of myopathic disease only
B) Rimmed vacuoles on gomori trichome stain on the periphery
C) Probably attributable to the drug’s effects on Tubulin
D) None of the above
True: C) Probably attributable to the drug’s effects on Tubulin
* Muscle biopsy shows elements of myopathic and NEUROPATHIC disease
* Rimmed vacuoles on gomori trichome stain that are more CENTRAL than those seen w/ IBM
D) None of the above
110
What is the most common cause of Arthrogryposis?
Werdnig-Hoffman motor neuron disease
111
Most common form of congenital clubfoot
A) Talipes equinus (plantar flexion of foot, ankle)
B) Talipes varus (inversion, clubfoot)
C) Talipes valgus (eversion, splayfoot)
D) Talipes calcaneus (dorsiflexion, ankle)
B) Talipes varus (inversion, clubfoot) - 75% of cases
112
The following are seen in the “core” of Central Core Myopathy EXCEPT?
A) Dense, amorphous condensation of myofibrils/myofibrillar material
B) Lacks mitochondria, organelles
C) Reduced (+) PAS reaction
D) Dark blue coloration (Gomori trichome stain)
E) Blue-green color
F) Lack of phosphorylase and oxidative enzymes
E) Blue-green color - this is the normal color of the peripheral myofibrils
113
What is the mutation associated with Nemaline myopathy?
ACTA1, AD
114
Which is NOT true of Nemaline Myopathy?
A) Muscles of the trunk and limbs are strikingly thin and hypoplastic
B) Facial, lingual, pharyngeal muscles are spared
C) A slender appearance, narrow face, open mouth, narrow, arched palate, and kyphoscoliosis are often seen
D) Rods are composed of material that resembles that of Z bands under EM, often actin filaments are attached
E) Type 1 fibers are smaller than normal
B) Facial, lingual, pharyngeal muscles are also strikingly thin and hypoplastic
115
Distinctive features of this congenital myopathy are ptosis and ocular palsies combined with weakness of facial, masticatory, lingual, pharyngeal, laryngeal, and cervical muscles in infants but not adults.
A) Central Core Myopathy
B) Nemaline Rod Myopathy
C) Centronuclear Myopathy
D) Myopathy with Tubular Aggregates
C) Centronuclear (Myotubular) Myopathy
116
What is seen in the EMG of Centronuclear Myopathy?
Myopathic pattern (usual) + positive sharp waves and fibrillation potentials, abundant spontaneous activity
