Lecture 34 - Other MD's

Question 1

What are the factors of classification of MD’s?

Answer 1

Age of onset

pattern of weakness

pattern of inheritance

involvement of other systems

Specific abnormalities on muscle biopsy

causative gene where identified

Question 2

What other systems can be involved in MD’s?

Answer 2

Brain

Musculoskeletal (spinal rigidity, scoliosis, joint contractures)

Endocrine systems

Eye (cataracts)

Question 3

After a muscle biopsy, what is done with the muscle?

Answer 3

immunohistochemistry

stain with fluorescent antibody staining for membrane proteins

Question 4

Myotonic dystrophy is the most common in __

Answer 4

adults

Question 5

Myotonic dystrophy is _______ ______t inhertance

Answer 5

autosomal dominan

Question 6

Myotonic dystrophy is a multisystem disorder affecting:

Answer 6

proximal and distal weakness and wasting

smooth muscle (constipations)

cognitive deficits

Cataracts

endocrine dysfunction

personality changes

Question 7

Myotonic dystrophy has 3 phenotypes, what are they?

Answer 7

congenital - most severe, resp.failure

classic - most common, muscle weakness presenting in adolescence

mild - cataract and

Question 8

Congenital Myotonic dystrophy babies will usually die in the first 4 weeks of life. If they survive, the babies will be

Answer 8

mentally retarded

respiratory insufficiencies

feeding deficiencies

Question 9

Myotonia is a characteristic found in some muscular dystrophies, what is it?

Answer 9

delayed relaxation of muscles after contraction

more often when cold and exercising

Question 10

True or False

There are Increased central nuclei in Myotonic dystrophy

Answer 10

true

Question 11

Mutant RNA transcribed from the expanded allele induce symptoms of the disease

RNA CUG expansions fold into hairpin like secondary structures which sequester specific proteins, resulting in….

Answer 11

depletion below a functional threshold

Question 12

Two important proteins bind to CUG repeats: MBNL1 and CCUGBP1

In Myotonic dystrophy, ____ is sequestered on CUG repeat-containing RNA, resulting in loss-of-function

Answer 12

In Myotonic dystrophy, MBNL1 is sequestered on CUG repeat-containing RNA, resulting in loss-of-function

Question 13

CUGBP1 is __-______, causing downstream effects such as disrupted regulation of alternative splicing, mRNA translation and mRNA stability

Answer 13

CUGBP1 is up-regulated, causing downstream effects such as disrupted regulation of alternative splicing, mRNA translation and mRNA stability

Question 14

Embryonic stage; MBNL1 nuclear levels ___, CUGBP1 levels ___

Answer 14

Embryonic stage; MBNL1 nuclear levels low, CUGBP1 levels high

Question 15

During development MBNL1 nuclear levels _____while CUGBP1 levels ______, inducing and embryonic-to-adult transition of downstream splicing targets

Answer 15

During development MBNL1 nuclear levels increases while CUGBP1 levels decrease, inducing and embryonic-to-adult transition of downstream splicing targets

Question 16

Limb-girdle muscular dsytrophies are generally ____muscle disorders

Answer 16

Limb-girdle muscular dsytrophies are generally progressive muscle disorders

Question 17

Limb-girdle muscular dsytrophies (LGMD) equally occur in

Answer 17

males and females 2-6th decade

Question 18

Is there CNS involvement with Limb-girdle muscular dystrophies?

Answer 18

no

Question 19

What are the tyopes of inheritance for Limb-girdle muscular dsytrophies?

Answer 19

AR - LGMD type 2 (much more common)
AD - LGMD, type 1
X-linked DMD/BMD

Question 20

What are the clinical clues to Limb-girdle muscular dsytrophies?

Answer 20

creatine kinase levels

muscle histology
- genetic testing, blood samples

Question 21

Limb-girdle muscular dsytrophies are associated with ____ viewable in histology

Answer 21

vacuoles

as well as Myotillin aggregates

Question 22

Presentation of FSHD?

Answer 22

AD
facial weakness - sleep with their eyes open
scapula winging
proximal arm weakness
Can't whistle
foot drop

Question 23

what is the selective muscle involvement in FSHD?

Answer 23

Weakness often pathy/asymmetrical

scapula and pectoral muscles affected early

lower 1/3 of abdomen - Beevor sign

heart/respiratory usually unaffected

Question 24

Is the gene for FSHD known?

Answer 24

no

Question 25

The penetrance is incomplete, so ..

Answer 25

30% all inherited cases are asymptomatic - symptoms more common in males

Question 26

FSHD can be linked to a deletion of ___ repeat sequence on chromosome 4

Answer 26

D4Z4

most people have 12-96 copies
FSHD patients, no more than 8

Question 27

The smaller the fragment of D4Z4 …

Answer 27

the more severe the FSHD - will onset earlier

Question 28

The problem with gene detaction for D4Z4 is that…

Answer 28

the gene probe detects changes in homologous areas on chromosome 4 & 10

Question 29

The is also _____ ______, meaning you can’t tell a mother that her next child will be okay, FSDH can be due to new mutations

Answer 29

Germline mosaicism: The precursor (germline) cells to ova and spermatazoa are a mixture (mosaic) of two or more genetically different cell lines.