Muscular dystrophies

Question 1

Patterns of weakness

Answer 1

1. ) Duchenne/Becker muscular dystrophy

2. )

Question 2

LGMD1A

Answer 2

Myotilinopathy
-impaired myotilin function

1. ) adult onset
2. ) symmetric weakness (starts in proximal legs)

Question 3

LGMD1B

Answer 3

Laminopathy
-impaired Lamin A/C protein function

1. ) childhood onset
2. ) limb contractures are common

Question 4

LGMD1C

Answer 4

Caveolinopathy
-reduced Caveolin-3 levels

1. ) childhood-adulthood
2. ) muscle hypertrophy (esp calf)
3. ) rippling muscle disease
4. ) NO respiratory involvement

Question 5

LGMD2A

Answer 5

Calpainopathy
-impaired Calpain-3 protein

1. ) contractures are common
2. ) NO muscle hypertrophy
3. ) NO cardiac involvement

Question 6

LGMD2B

Answer 6

Dysferlinopathy
-reduced dysferlin levels

1. ) Miyoshi Distal Myopathy–> symmetric calf wasting
2. ) No cardiac
3. ) No respiratory
4. ) Diamond Sign: patients attempt to sit down, feet firm on ground

Question 7

LGMD2C-F

Answer 7

Sarcoglycanopathies
-mutations affecting sarcoglycan complex

1. ) childhood onset
2. ) calf/tongue hypertrophy
3. ) contractures are common
4. ) hearing loss

Question 8

LGMD2I

Answer 8

Fukutin-related proteinopathy

• white population and Japan
• impaired fukutin-related protein function

1. ) muscles hypertrophy (calves, tongue) common
2. ) contractures and scoliosis

Question 9

LGMD2J

Answer 9

Titinopathy
-reduced Titin levels

1.) distal myopathy
“Finnish distal myopathy”
2.) No cardiac
3.) No respiratory

Question 10

LGMD2K/M-P

Answer 10

Dystroglycanopathies
-dystroglycanopathy

1. ) muscle hypertrophy (calves, tongue)
2. ) occasional microcephaly, vermis hypoplasia, polymigrogyria
3. ) joint contractures

Question 11

LGMD2L

Answer 11

Anoctaminopathy
-mutations affecting anoctamin protein

1. ) asymmetric
2. ) atrophied muscles (quads, biceps, lower legs)
3. ) calf hypertrophy (+/-)
4. ) No cardiac, no respiratory

Question 12

LGMD2V

Answer 12

Pompe’s Disease

-acid glucosidase enzyme deficiency

Question 13

Duchenne/Becker’s dystrophy

Answer 13

Dystrophin

• X-linked
• genetic testing for dystrophin mutations

1. ) symmetric, proximal weakness
2. ) onset between 2-5 years of age
3. ) many symptoms…..prominent neck flexor weakness, calf/tongue hypertrophy
4. ) Gower’s sign
5. ) cardiac features (dilated cardiomyopathy)
6. ) restrictive lung disease
7. ) cognitive issues
8. ) might blindness (due to dystrophin in reina)
9. ) elevated LFTs

Becker’s: milder form

Question 14

Duchenne/Becker-Treatment

Answer 14

-Prednisone 0.75mg/kg/d

Question 15

Emery-Dreifuss Muscular Dystrophy

Answer 15

Mutation in Emerin gene-type 1

• absent emerin protein
• X-linked

1. ) contractures
2. ) humeroperoneal weakness–> DELTOIDS SPARED
3. ) cardiac involvement

Lamin A/C protein function-type 2/3

• impaired Lamin A/C
• AD or AR

Same clinical stuff as above–>contractures onset after weakness

Question 16

Fascioscapulohumeral Muscular Dystrophy

Answer 16

FSHD1 and FSHD2

• disinhibition of DUX4 gene–> toxic gain of function
• -> AD

1. ) loss of D4Z4 repeated units (normal >10, FHSD1=1-10)
2. ) Polymorphism on mutated allele

Clinical

1. ) Deltoid often preserved
2. ) NO ptosis, EOM or dysphagia
3. ) Contractures NOT common
4. ) decreased brow furrow
5. ) inability to bury lashes on eye closure
6. ) flattened pucker
7. ) Pec wasting, and exaggerated axillary crease
8. ) protuberant abdomen
9. ) Popeye arms (biceps/triceps wasting)
10. ) shoulder hump sign+weak shoulder shrug
11. ) scapular winging
12. ) NO cardiac involvement
13. ) extramuscular: hearing loss, retinal vascular changes, Coat’s disease, cognitive deficits

BEEVOR SIGN: asymmetry of abdo muscle; pathognomonic for FSHD

Question 17

Distal weakness

Answer 17

1. ) IBM
2. ) Myotonic dystrophy
3. ) Finnish distal myopathy (titinopathy)
4. ) Miyoshi distal myopathy (dysferlinopathy)
5. ) Welander distal myopathy