Myotonic Dystrophy

Monogenic (Mendelian): 100%, DM1 (DMPK CTG expansion) and DM2 (CNBP CCTG expansion); shows anticipation^[1]

Inheritance: Autosomal dominant with anticipation, repeat length increases and disease severity worsens in successive generations.^[2]

Familial proportion: Nearly 100% of cases are inherited from an affected parent; de novo repeat expansions are extremely rare. First-degree relatives (parent, sibling, child) have a 50% risk of inheriting the mutation. Offspring of affected mothers are at particular risk of the severe congenital form (DM1) due to maternal anticipation.^[2]

DM1: DMPK gene (CTG repeat expansion); normal <37 repeats; pathogenic ≥50 repeats

DM2: CNBP gene (CCTG repeat expansion); typically milder cardiac involvement than DM1

Estimated prevalence 1 in 8,000, the most common adult-onset muscular dystrophy worldwide.^[1]

DM1 (Steinert disease) is more common and severe than DM2; cardiac disease accounts for approximately 30% of deaths in DM1.^[1]

Confirming the diagnosis: genetic testing, a CTG repeat expansion in DMPK confirms DM1; a CCTG expansion in CNBP (ZNF9) confirms DM2. DM1 carries the greater cardiac (conduction-disease) risk.^[1]

Neuromuscular: Myotonia (delayed muscle relaxation), distal weakness, facial weakness

Cardiac (major cause of death):

• Progressive conduction disease (PR prolongation → AV block)
• Atrial arrhythmias, ventricular arrhythmias
• Cardiomyopathy (less common, late feature)
• Sudden death (even with pacemaker)

Other: Cataracts, endocrinopathy, cognitive impairment

ECG: PR prolongation, AV block, QRS widening, atrial arrhythmias, annual minimum^[3]

Holter: Annual 24-hour Holter to detect paroxysmal arrhythmias^[2]

Echo: Assess LV function (cardiomyopathy is a late feature)

EP study: Consider if syncope or high-risk ECG features, HV interval ≥70ms predicts need for pacemaker^[1]

Genetic testing: CTG/CCTG repeat sizing (diagnostic)

1. General measures:

• Annual ECG minimum (6-monthly if PR >200ms or QRS >120ms)
• 24h Holter annually
• Genetic counselling and family cascade testing, see the Genetic Testing page

2. Medical therapy:

• No disease-modifying pharmacological therapy exists for the conduction disease itself; standard guideline-directed heart failure therapy applies if cardiomyopathy develops

3. Device therapy:

• Pacemaker: standard indications (2nd/3rd degree AV block, symptomatic bradycardia); consider if HV interval ≥70ms on EP study
• ICD: secondary prevention; primary prevention if high-risk features + cardiomyopathy
• Note: pacemaker does NOT eliminate SCD risk (ventricular arrhythmias still occur)

4. Advanced heart failure and/or transplant referral:

• Standard advanced-heart-failure pathways apply if cardiomyopathy progresses to refractory heart failure; respiratory involvement often requires joint management with respiratory medicine

• Progressive conduction disease: PR and QRS prolongation advancing to high-grade AV block and sudden death, which can occur without overt cardiomyopathy and is a major cause of mortality^[1]
• Atrial flutter or fibrillation and ventricular arrhythmia: sudden death can occur even after pacing, hence the ICD versus pacemaker debate
• Dilated cardiomyopathy and heart failure: less common, and later
• Anaesthetic and sedation sensitivity: with respiratory compromise

Cardiac disease accounts for ~30% deaths (sudden death, heart failure)

Respiratory failure also major cause of death

Based on ESC 2022 Ventricular Arrhythmia guidelines and myotonic dystrophy cardiac data^[3][1].

Advanced / complicated = PR/QRS prolongation or other conduction disease, syncope, documented arrhythmia, or a device in situ.

Genotype-positive / phenotype-negative (G+/P−) = a confirmed pathogenic-variant carrier with no overt disease expression yet.

	Genotype+ / Phenotype−	Uncomplicated / Stable	Advanced / Complicated
Frequency	Annual (monitor for conduction disease)	Annual	Every 6 months
Clinical review	Symptoms, syncope	Syncope, palpitations, symptoms	As above + device check
ECG	Annual (PR & QRS)	Annual 12-lead (PR & QRS trend)	Each visit
Holter / ambulatory	Periodic	Annual (AF, conduction, VT)	6-monthly or symptom-directed
Echocardiography	Every 1–3 years	Every 1–3 years	Annual
EPS / device	If conduction disease emerges	Consider if PR/QRS prolongation or syncope	As indicated

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

• High index of suspicion for conduction disease - can progress rapidly^[1]
• Pacemaker prevents bradycardia death but NOT ventricular arrhythmias^[1]
• Anesthetic risk - avoid depolarizing agents, prolonged recovery^[1]
• Pregnancy: genetic counselling essential (anticipation → more severe in offspring)