Myotonic Dystrophy Flashcards
Myotonic dystrophy type 1 - incidence
most common inherited neuromuscular disorder in adults - 1:7,500-8,000
Myotonic dystrophy type 1 - clinical features
depends on the size of the expansion
Myotonic dystrophy type 1 - genetic cause & inheritance
Caused by trinucleotide repeat expansion in DMPK gene on chromosome 19, autosomal dominant
Myotonic dystrophy type 1 - etiology
Expansion creates toxic expanded RNA that leads to abnormal splicing of other genes
Mild DM1 - clinical features & repeat size
50 - ~150 repeat expansion; cataracts, mild myotonia and muscle weakness, diabetes
Mild DM1 - age of onset
20-70 years, but average age of onset is after 40
Prognosis of mild DM1
Normal lifespan
Classic or “adult onset” DM1 - clinical features & repeat size
~150-1,000 repeat expansion; muscle weakness & wasting, myotonia, cataracts, cardiac conduction abnormalities, respiratory weakness, endocrinopathies, fatigue and tiredness
Classic or “adult onset” DM1 - age of onset
Onset in adolescence or early adulthood (20-30s)
Classic or “adult onset” DM1 - lifespan
May have shortened lifespan (late 40s to 50s)
Childhood “Juvenile Onset” DM1 - clinical features & repeat size
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
Childhood “Juvenile Onset” DM1 - onset
before adolescence, but no signs at birth
Congenital DM1 - clinical features & repeat size
greater than 1,000 repeat expansion; severe generalized weakness at birth, respiratory insufficiency, intellectual disability, prenatal abnormalities such as polyhydramnios, decreased fetal movement
Congenital DM1 - onset & prognosis
congenital onset, shortened lifespan. 25% die before 18 months, 50% die before mid 30s
Suggestive findings of DM1
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
Testing for DM1
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
Cancer risk for DM1
cancer is the 3rd leading cause of death in individuals with DM1. Statistically significant increased risk for endometrial, ovarian, brain, colon, and polomatricoma cancers
DM2 - clinical features
progressive muscle weakness (proximal muscles of lower extremities), myotonia, cataracts, heart conduction defects, respiratory problems, gastrointestinal problems, endocrine abnormalities
DM2 - age of onset
usually in adulthood, in the 40s, but can occur earlier or later
DM2 - severity
tend to be milder than DM1, but can still cause significant disability
DM2 - genetic cause and inheritance
Tetranucleotide repeat expansion in the CNBP gene on chromosome 3 - AD
Testing for DM2
Molecular - heterozygous expansion of tetranucleotide repeat in CNBP
