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Neurology
Genetics

Myotonic Dystrophy (DM1 & DM2)

High EvidenceUpdated: 2025-12-24

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Red Flags

  • Cardiac conduction block (Sudden death risk)
  • General anaesthesia (Respiratory failure risk)
  • Severe congenital form (Floppy infant)
Overview

Myotonic Dystrophy (DM)

1. Clinical Overview

Summary

Myotonic Dystrophy (DM) is the most common adult-onset muscular dystrophy. It is a multisystem disorder characterized by Myotonia (inability to relax muscles after contraction), progressive muscle weakness and wasting, cataracts, and cardiac conduction defects. There are two main types:

  • Type 1 (DM1): Evaluation of CTG repeats in the DMPK gene. Severe, affects distal muscles, face, and has a congenital form.
  • Type 2 (DM2): Mild, proximal weakness. The condition is Autosomal Dominant with Anticipation (worsens in successive generations). Management is supportive, but cardiac surveillance (annual ECG/Holter) is critical to prevent sudden death from Heart Block. Modafinil helps the excessive daytime sleepiness. [1,2]

Key Facts

  • Genetics: DM1 is a Nucleotide Repeat Expansion disorder (CTG) on Chr 19.
  • The "Hatchet Face": Wasting of temporalis and masseter muscles gives a narrow, mournful facial appearance.
  • Myotonia: Difficulty letting go of a handshake. Worsened by cold.
  • Multisystem:
    • Eye: "Christmas Tree" Cataracts.
    • Heart: Conduction block (1st degree -> Complete).
    • Endocrine: Diabetes, Testicular atrophy, Frontal Balding.
    • GI: Dysphagia, Pseudo-obstruction.
    • Brain: Apathy, hypersomnolence.

Clinical Pearls

"The Percussion Myotonia": Tap the Thenar eminence (thumb base) with a tendon hammer. The thumb will adduct and flex, and relax very slowly (over 5-10 seconds). This is diagnostic at the bedside.

"Balding and Hatchet Face": If you see a patient with frontal balding, a narrow face, and they can't let go of your hand... it's DM1 until proven otherwise.

"Sudden Death": A patient with DM1 who calls with "dizziness" or "palpitations" needs an urgent ECG. Pacemakers save lives here.

2. Epidemiology

Incidence

  • Prevalence: 1 in 8,000 (DM1).
  • Onset: Any age (Congenital to Late Adult).
  • Inheritance: Autosomal Dominant.
3. Pathophysiology

Genetics (DM1)

  • Gene: DMPK (Dystrophia Myotonica Protein Kinase).
  • Locus: Chromosome 19q13.
  • Defect: Expansion of a CTG trinucleotide repeat in the 3' untranslated region.
  • Mechanism: "RNA Toxicity". The expanded RNA transcripts accumulate in the nucleus and sequester splicing factors (like Muscleblind-like 1 [MBNL1]). This causes mis-splicing of other genes (e.g. Chloride channel -> Myotonia; Insulin receptor -> Diabetes).
  • Repeat Numbers:
    • Normal: 5-34 repeats.
    • Mild: 50-150.
    • Classic: 100-1000.
    • Congenital: >1000.

Genetics (DM2)

  • Gene: CNBP (ZNF9).
  • Defect: CCTG tetranucleotide repeat.
  • Features: Milder ("PROMM" - Proximal Myotonic Myopathy). No congenital form.
4. Clinical Presentation

Muscular

  1. Myotonia: Stiff muscles. Hands "lock" after grip. Tongue stiffness.
  2. Weakness (DM1):
    • Face: Ptosis, Facial weakness (myopathic facies).
    • Neck: Sternocleidomastoid wasting (Swan neck).
    • Distal Limbs: Hand grip, Foot drop.
  3. Weakness (DM2): Proximal (Hips/Shoulders).

Extramuscular (Systemic)

  1. Cardiac:
    • Conduction defects (PR prolongation, bundle branch block).
    • Arrhythmias (AF, VT).
    • Cardiomyopathy (rare).
  2. Ophthalmic:
    • Cataracts: Early onset. Posterior subcapsular. "Christmas Tree" appearance (polychromatic).
    • Ptosis.
  3. Endocrine:
    • Insulin resistance (Diabetes).
    • Hypogonadism (Testicular atrophy, infertility).
    • Frontal Balding (Men).
  4. Neurological (CNS):
    • Excessive Daytime Sleepiness (Central origin).
    • Apathy / Executive dysfunction ("Avoidant" personality).
  5. Gastrointestinal:
    • Dysphagia.
    • Constipation / Pseudo-obstruction (Smooth muscle involvement).

Congenital DM1

Occurs when a mother with DM1 passes a massive expansion (>1000 repeats) to the fetus.
Common presentation.
Features
Severe hypotonia ("Floppy Infant"). Respiratory failure at birth. Facial diplegia ("Tented mouth"). Intellectual disability. Club foot.
5. Investigations

Genetic Testing (Gold Standard)

  • PCR: Detects small expansions.
  • Southern Blot: Detects large expansions (>100 repeats).
  • Anticipation: Genetic counselling is crucial as the disease gets worse in the next generation.

Cardiac Surveillance

  • ECG: Annual. Look for PR > 200ms or QRS > 120ms.
  • Holter Monitor: If symptoms or ECG abnormalities.

Neurophysiology (EMG)

  • "Dive Bomber" Sound: The classic audio sign of myotonic discharges on EMG. High frequency discharges that wax and wane in amplitude and frequency.
6. Management

Management Algorithm

        DIAGNOSIS CONFIRMED
                ↓
    ┌──────┬────────┬──────────┐
  HEART   EYES    MUSCLE     CNS
    ↓      ↓        ↓          ↓
 Annual  Cataract  Mexiletine Modafinil
 ECG     Surgery   (for      (Sleepiness)
                   Myotonia)

1. Cardiac

  • Pacemaker / ICD: Low threshold for insertion if conduction block found.
  • Monitor closely.

2. Myotonia

  • Often does not need treatment (patients adapt).
  • If severe: Mexiletine (Sodium channel blocker).
  • Caution: Mexiletine is anti-arrhythmic but pro-arrhythmic in structural heart disease. Consult Cardiology.

3. Respiratory

  • NIV: For nocturnal hypoventilation.
  • Evaluate before any General Anaesthetic (high risk of post-op respiratory failure).

4. Excessive Sleepiness

  • Modafinil: Very effective for the central hypersomnolence.
7. Deep Dive: RNA Toxicity Mechanism

"The Toxic Clump." DM1 is the prototype of an RNA-mediated disease.

  • The DNA mutation (CTG expansion) is transcribed into mRNA.
  • This mutant mRNA forms "hairpin" structures in the nucleus.
  • These hairpins act like a sponge, soaking up splicing proteins (MBNL1).
  • Consequence: Other genes are spliced incorrectly (returning to fetal splice patterns).
    • ClC-1 Chloride Channel: Spliced wrong -> Less chloride conductance -> Membrane hyperexcitability -> Myotonia.
    • Insulin Receptor: Spliced wrong -> Diabetes.
8. Deep Dive: Anaesthetic Risks

"The induction that doesn't end." Patients with DM1 are a nightmare for anaesthetists if undiagnosed.

  1. Respiratory Failure: Extreme sensitivity to opiates and sedatives.
  2. Myotonia: Suxamethonium (depolarizing blocker) can trigger massive generalized myotonic contracture -> Impossible to ventilate.
  3. Arrhythmia: Volatile agents can trigger heart block. Rule: Always declare "Family history of muscle disease" before surgery.
9. Surgical Atlas: Cataract Surgery

"The Christmas Tree."

  • The cataract in DM1 is unique.
  • Appearance: Iridescent, polychromatic crystals in the cortex ("Christmas Tree").
  • Progression: Evolves into a standard posterior subcapsular cataract.
  • Surgery: Standard Phacoemulsification.
  • Caveat: Weak Zonules? (Lens may be unstable).
10. Technical Appendix: Anticipation

"Getting worse with time."

  • Definition: The phenomenon where a genetic disorder becomes more severe and starts at an earlier age in successive generations.
  • Mechanism: The CTG repeat is unstable during meiosis (especially maternal meiosis). It expands.
    • Grandparent: 60 repeats (Cataracts only).
    • Parent: 400 repeats (Classic DM1).
    • Child: 1500 repeats (Congenital DM1).
    • Note: Paternal transmission usually leads to stable or smaller expansions. Maternal transmission leads to massive expansion.
11. Prognosis
  • Congenital: High mortality in infancy (Respiratory). If they survive, moderate to severe disability.
  • Classic: Reduced life expectancy (approx 50-60 years). Death usually from Respiratory failure or Cardiac arrhythmia.
  • Mild: Normal life expectancy.
12. Patient Explanation

What is Myotonic Dystrophy?

It is a genetic condition affecting muscles and other organs. The main symptom is "Myotonia" - stiffness where muscles can't relax quickly (like gripping a door handle and getting stuck).

Is it just muscles?

No. It affects the heart (electrical wiring), eyes (cataracts), and energy levels (sleepiness). We need to check your heart once a year.

Can I have children?

There is a 50% chance of passing it on. Crucially, if you are a mother with the condition, there is a risk of having a baby with a very severe form ("Congenital"). Genetic counselling is essential before pregnancy.

13. References
  1. Turner C, Hilton-Jones D. The myotonic dystrophies: diagnosis and management. J Neurol Neurosurg Psychiatry. 2010.
  2. Harper PS. Myotonic Dystrophy. 3rd ed. London: WB Saunders; 2001.
14. Examination Focus

Common Exam Questions

1. Genetics:

  • Q: What is the inheritance pattern and genetic defect?
  • A: Autosomal Dominant. CTG repeat expansion in DMPK gene on Chr 19.

2. Physical Signs:

  • Q: Demonstrate Percussion Myotonia.
  • A: Tap the thenar eminence. Watch for adduction/flexion of the thumb and slow relaxation.

3. Complications:

  • Q: What is the major cause of sudden death?
  • A: Cardiac conduction block (Complete Heart Block) or VT.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.

Last updated: 2025-12-24

At a Glance

EvidenceHigh
Last Updated2025-12-24

Red Flags

  • Cardiac conduction block (Sudden death risk)
  • General anaesthesia (Respiratory failure risk)
  • Severe congenital form (Floppy infant)

Clinical Pearls

  • **"The Percussion Myotonia"**: Tap the Thenar eminence (thumb base) with a tendon hammer. The thumb will adduct and flex, and relax very slowly (over 5-10 seconds). This is diagnostic at the bedside.
  • **"Balding and Hatchet Face"**: If you see a patient with frontal balding, a narrow face, and they can't let go of your hand... it's DM1 until proven otherwise.
  • **"Sudden Death"**: A patient with DM1 who calls with "dizziness" or "palpitations" needs an urgent ECG. Pacemakers save lives here.
  • Myotonia; Insulin receptor -
  • Less chloride conductance -

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines