PATH - Muscular Dystrophies

Question 1

Duchenne Muscular dystrophy

Answer 1

X-linked disorder

typically due to *frameshift or
*nonsense mutations–>truncated *dystrophin
protein–>inhibited muscle regeneration

Weakness begins in pelvic girdle muscles and progresses superiorly.

Pseudohypertrophy of
calf muscles due to fibrofatty replacement of muscle

*Gower maneuver

*Dilated cardiomyopathy is common cause of
death

INC CK and aldolase are seen; Western blot and
muscle biopsy confirm diagnosis

Question 2

Becker Muscular dystrophy

Answer 2

X-linked disorder

typically due to *non-frameshift insertions in *dystrophin gene (partially functional instead of truncated).

Less severe than Duchenne.

Onset in adolescence or early adulthood.

Question 3

Myotonic type 1

Answer 3

Autosomal dominant.

*CTG trinucleotide repeat
expansion in the DMPK gene–>abnormal expression of myotonin protein kinase–>myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia

My Tonia, My Testicles (testicular atrophy), My Toupee (frontal balding), My Ticker (arrhythmia).

Question 4

Fragile X syndrome

Answer 4

X-linked dominant

Trinucleotide repeat in *FMR1 gene methylation–>DEC expression.

The 2nd most common cause of genetic intellectual disability (after Down syndrome)

Findings: post-pubertal
macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse.

Trinucleotide repeat disorder (CGG)n.

Fragile X = eXtra large testes, jaw, ears.