Myotonic Dystrophy

Question 1

Myotonic dystrophy type 1 - incidence

Answer 1

most common inherited neuromuscular disorder in adults - 1:7,500-8,000

Question 2

Myotonic dystrophy type 1 - clinical features

Answer 2

depends on the size of the expansion

Question 3

Myotonic dystrophy type 1 - genetic cause & inheritance

Answer 3

Caused by trinucleotide repeat expansion in DMPK gene on chromosome 19, autosomal dominant

Question 4

Myotonic dystrophy type 1 - etiology

Answer 4

Expansion creates toxic expanded RNA that leads to abnormal splicing of other genes

Question 5

Mild DM1 - clinical features & repeat size

Answer 5

50 - ~150 repeat expansion; cataracts, mild myotonia and muscle weakness, diabetes

Question 6

Mild DM1 - age of onset

Answer 6

20-70 years, but average age of onset is after 40

Question 7

Prognosis of mild DM1

Answer 7

Normal lifespan

Question 8

Classic or “adult onset” DM1 - clinical features & repeat size

Answer 8

~150-1,000 repeat expansion; muscle weakness & wasting, myotonia, cataracts, cardiac conduction abnormalities, respiratory weakness, endocrinopathies, fatigue and tiredness

Question 9

Classic or “adult onset” DM1 - age of onset

Answer 9

Onset in adolescence or early adulthood (20-30s)

Question 10

Classic or “adult onset” DM1 - lifespan

Answer 10

May have shortened lifespan (late 40s to 50s)

Question 11

Childhood “Juvenile Onset” DM1 - clinical features & repeat size

Answer 11

Greater than 800 repeat expansion; cognitive and behavioral problems, muscle weakness and myotonia, anxiety and mood disorders, some may have arrhythmia with physical exertion, around 10% have cardiomyopathy and heart failure

Question 12

Childhood “Juvenile Onset” DM1 - onset

Answer 12

before adolescence, but no signs at birth

Question 13

Congenital DM1 - clinical features & repeat size

Answer 13

greater than 1,000 repeat expansion; severe generalized weakness at birth, respiratory insufficiency, intellectual disability, prenatal abnormalities such as polyhydramnios, decreased fetal movement

Question 14

Congenital DM1 - onset & prognosis

Answer 14

congenital onset, shortened lifespan. 25% die before 18 months, 50% die before mid 30s

Question 15

Suggestive findings of DM1

Answer 15

eyelid ptosis, distal weakness especially in fingers and wrist flexors w/o contractures, myotonia, presenile cataracts; neonates with: hypotonia, facial weakness, generalized weakness, positional malformations, respiratory insufficiency

Question 16

Testing for DM1

Answer 16

Molecular testing - PCR, southern blot
Electromyography - evaluate for electrical myotonia (abnormal muscle activity when a small needle is inserted into the muscle)
Serum CK concentration - may be elevated if there is weakness
Muscle biopsy

Question 17

Cancer risk for DM1

Answer 17

cancer is the 3rd leading cause of death in individuals with DM1. Statistically significant increased risk for endometrial, ovarian, brain, colon, and polomatricoma cancers

Question 18

DM2 - clinical features

Answer 18

progressive muscle weakness (proximal muscles of lower extremities), myotonia, cataracts, heart conduction defects, respiratory problems, gastrointestinal problems, endocrine abnormalities

Question 19

DM2 - age of onset

Answer 19

usually in adulthood, in the 40s, but can occur earlier or later

Question 20

DM2 - severity

Answer 20

tend to be milder than DM1, but can still cause significant disability

Question 21

DM2 - genetic cause and inheritance

Answer 21

Tetranucleotide repeat expansion in the CNBP gene on chromosome 3 - AD

Question 22

Testing for DM2

Answer 22

Molecular - heterozygous expansion of tetranucleotide repeat in CNBP