Makindo Medical Notes

🧬 About

• Myotonic dystrophy (Dystrophia Myotonica) is the most common muscular dystrophy of adult life.
• It is an autosomal dominant condition with variable penetrance, showing progressive multisystem involvement.

⚖️ Aetiology

• Type 1 (DM1): Caused by expanded trinucleotide (CTG) repeat in the 3’ untranslated region of the DMPK gene (chromosome 19). Abnormal if >34 repeats. Demonstrates anticipation → earlier, more severe onset in successive generations. Prenatal testing possible.
• Type 2 (DM2 / Proximal Myotonic Myopathy): Due to expanded CCTG repeat in an intronic region of the ZNF9 gene (chromosome 3). Presents in young adults with proximal weakness (neck/finger flexors, hips), myotonia, cataracts. Generally milder than DM1.
• Anticipation: Disease severity increases down generations due to further repeat expansions.

🧑‍⚕️ Clinical Features

• Characteristic appearance: frontal balding, ptosis, facial muscle wasting (temporalis, SCM).
• Progressive muscle weakness and atrophy – usually mild and slowly progressive.
• Cardiac conduction defects (PR prolongation, arrhythmias) → may require pacemaker (distinct from cardiomyopathy seen in Duchenne/Becker).
• Cataracts (often early, “Christmas tree” opacities).
• Endocrine/metabolic: impaired glucose tolerance, insulin resistance.
• Respiratory muscle weakness → risk of sleep apnoea, hypoventilation.
• Cognitive involvement: learning difficulties, reduced IQ in ~50%.
• GI dysmotility: dysphagia, constipation, pseudo-obstruction.
• Immunological abnormalities: low IgG levels in some cases.

Young man with DM1: frontal baldness, bilateral ptosis, and wasting of temporalis, facial, and sternocleidomastoid muscles.

📊 Comparison of Myotonic Dystrophy Type 1 and Type 2

Feature	Type 1 (DM1)	Type 2 (DM2)
Genetic Mutation	CTG trinucleotide repeat in DMPK gene (chromosome 19)	CCTG tetranucleotide repeat in ZNF9 gene (chromosome 3)
Onset	Congenital, childhood, or adult-onset (variable)	Typically young adulthood
Anticipation	Prominent — worsens with each generation	Mild/absent anticipation
Distribution of Weakness	Distal & facial (ptosis, SCM, temporalis, hand muscles)	Proximal (hip flexors, neck flexors, finger flexors)
Myotonia	Prominent, often disabling	Present but usually milder
Systemic Features	Cataracts, insulin resistance, cardiac conduction defects, GI dysmotility, cognitive impairment	Cataracts, muscle pain, less cardiac involvement, rare cognitive effects
Severity	More severe, multisystem, congenital forms possible	Milder, slower progression, rarely life-threatening

🧪 Investigations

• Genetic Testing: Gold standard – identifies repeat expansion.
• CK (Creatine Kinase): May be mildly elevated (2–10× normal).
• Muscle Biopsy: Myofibre atrophy + central nuclei.
• EMG: Classic myotonic discharges (waxing and waning potentials).
• ECG: PR prolongation, atrial flutter, ventricular arrhythmias.
• Other labs: Low IgG; glucose tolerance tests.

💊 Management

• Myotonia: Phenytoin (100 mg TDS) preferred. Mexiletine sometimes used. ⚠️ No treatment halts progressive weakness.
• Cardiac: Annual ECG, 24-hr Holter, cardiology review. Pacemaker/ICD if significant conduction disease.
• Respiratory: Avoid respiratory depressants. Consider CPAP for sleep apnoea.
• Obstetric: Risk of ineffective uterine contractions; multidisciplinary delivery planning.
• Supportive: Speech/swallow therapy, physiotherapy, cataract surgery, endocrine screening.

🛑 Anaesthetic Precautions

• Avoid suxamethonium → prolonged contraction & dangerous myotonia.
• Non-depolarising relaxants = safe at usual doses; reversal agents tolerated.
• Mechanical/electrical stimuli (diathermy) may trigger myotonia → use caution.
• Regional anaesthesia often preferred.

📌 Key Points

• DM = a multisystem disorder (muscle, eye, heart, endocrine, respiratory, cognitive, GI).
• Anticipation leads to earlier/more severe disease in successive generations.
• Cardiac monitoring is essential → conduction disease is a major cause of sudden death.
• No curative therapy; management is supportive and multidisciplinary.

Cases — Myotonic Dystrophy (Dystrophia Myotonica)

• Case 1 — Adult with grip myotonia ✋: A 28-year-old man presents with difficulty releasing his grip after shaking hands. He also reports progressive weakness of facial and distal limb muscles. Exam: long thin face, frontal balding, ptosis, and “hatchet” facies. EMG: myotonic discharges. Diagnosis: Myotonic dystrophy type 1. Managed with symptomatic therapy (physio, speech therapy) and cardiac monitoring.
• Case 2 — Multisystem involvement ❤️👁️: A 40-year-old woman with known myotonic dystrophy presents with daytime somnolence, cataracts, and palpitations. ECG: conduction block. Exam: distal weakness, myotonia on percussion of thenar eminence. Diagnosis: multisystem complications of myotonic dystrophy. Managed with cataract surgery, pacemaker insertion if conduction disease, and endocrine screening (thyroid, diabetes).
• Case 3 — Congenital form 👶: A newborn boy is floppy at birth with severe hypotonia and respiratory distress. Mother has mild muscle weakness and early cataracts. Baby requires ventilatory support. Genetic testing: CTG repeat expansion in DMPK gene. Diagnosis: congenital myotonic dystrophy (maternal transmission). Managed with NICU care and long-term multidisciplinary follow-up.

Teaching Point 🩺: Myotonic dystrophy is the most common adult muscular dystrophy. - Type 1 (DMPK gene, CTG repeat) → distal weakness, grip myotonia, cataracts, cardiac conduction defects. - Type 2 (CNBP gene, CCTG repeat) → proximal weakness, later onset. Inheritance: autosomal dominant, anticipation seen (earlier/severe disease in successive generations). Always monitor for respiratory, cardiac, and endocrine complications.