Last updated 12d ago
A 30-year-old man has difficulty releasing his grip after a handshake. He has frontal balding, bilateral ptosis, and cataracts. His mother and grandmother are also affected.
AD; CTG repeat expansion in DMPK (3'UTR)
- Normal: 5-34 repeats
- Prevariant: 35-49
- Mild: 50-150
- Classic: 100-1000
- Congenital: >1000
- Myotonia (delayed muscle relaxation)
- Progressive muscle weakness (distal > proximal)
- Facial weakness ("hatchet face"), ptosis
- Cataracts (posterior subcapsular)
- Cardiac conduction defects
- Cognitive/behavioral
- Insulin resistance, testicular atrophy
Congenital DM1: Maternal transmission, severe hypotonia, respiratory failure, intellectual disability
Anticipation: Striking - especially maternal (congenital form)
- Clinical clues: grip and percussion myotonia, distal weakness, frontal balding, ptosis, and posterior subcapsular cataracts
- Targeted testing for the CTG repeat expansion in DMPK (standard PCR plus Southern blot or triplet-repeat-primed PCR for large alleles)
- EMG shows myotonic discharges, but molecular testing is confirmatory
- Larger repeats correlate with earlier onset and severity; counsel on anticipation and the maternally transmitted congenital form
- Annual ECG/cardiology surveillance for conduction block and arrhythmia; pacemaker/ICD when indicated (a leading cause of death)
- Pulmonary monitoring and treatment of respiratory weakness and sleep-disordered breathing
- Mexiletine for symptomatic myotonia; periodic cataract and diabetes screening
- Anesthesia precautions: high risk of respiratory and cardiac complications; avoid depolarizing agents and minimize opioids/sedatives
"MyoToniC = CTG": The trinucleotide repeat (CTG) is embedded in the name. Cataracts / Cheek wasting / Cardiac arrhythmia, Toupee (early balding in men), Gonadal atrophy.
"MyoToxic dystrophy": CTG expansion in 3' UTR of DMPK produces toxic mRNA.
"Myotonic dUsTRophy" (UTR): The CTG repeat sits in the 3' UTR of DMPK.
"Examine the Mother in Myotonic": Congenital DM1 is almost always maternally transmitted, so examine the mother for signs of disease. (Non-congenital DM1 expansions are frequently transmitted by either parent.)
"MeTrONome in MyoTONic": Cardiac conduction defects and arrhythmias are the #2 cause of death (#1 is respiratory failure).