Progressive Weakness

Clinical Vignette

A 40-year-old man presents with progressive weakness in his hands. Please examine his face and upper limbs.

Positive Findings:

Facial Features:

  • Myopathic Facies: Elongated, expressionless face with hollowed cheeks.
  • Frontal Balding: Notable thinning of hair over the forehead.
  • Ptosis: Bilateral drooping of the eyelids.
  • Temporalis Muscle Wasting: Hollowing of the temples.
  • Smooth Forehead: Loss of facial muscle tone.

Hands:

  • Grip Myotonia: Slow release of grip after shaking hands or clenching a fist.
  • Percussion Myotonia: Tapping the thenar eminence produces a dimple with slow relaxation.
  • Weakness and Wasting: Distal muscle involvement with atrophy of intrinsic hand muscles.

Additional Signs:

  • Finger prick marks from blood glucose testing.
  • Dysarthria: Nasal, slurred speech due to tongue and pharyngeal muscle involvement.
  • Absent or reduced tendon reflexes in the upper limbs.
  • Systemic Signs: Pacemaker scar, testicular atrophy and cataracts (check for red reflex or slit lamp evaluation).

Relevant Negative Findings:

  • No evidence of fatiguability.
  • No sensory loss.
  • No proximal muscle weakness.
  • No signs of respiratory distress or decompensated cardiac failure.

What is the most likely diagnosis?

The findings are consistent with Myotonic Dystrophy Type 1 (DM1), an autosomal dominant condition associated with myotonia, distal muscle weakness, and systemic involvement.

What is your differential diagnosis?

1. Inherited Myopathies:

  • Facioscapulohumeral Dystrophy: Myopathic facies without myotonia.
  • Limb-Girdle Muscular Dystrophy: Proximal muscle weakness and no myotonia.

2. Neurological Disorders:

  • Myasthenia Gravis: Fatiguability with ptosis but no myotonia.
  • Neuromyotonia (Isaacs’ Syndrome): Continuous muscle activity, rare compared to myotonic dystrophy.

3. Systemic and Mitochondrial Conditions:

  • Mitochondrial Myopathy: May include diabetes, ptosis, and myopathy but no myotonia.

How would you investigate this patient?

1. Primary Diagnostic Tests:

  • Genetic Testing: Detects CTG trinucleotide repeat expansion in the DMPK gene on chromosome 19.
  • Electromyography (EMG): Demonstrates myotonia, producing characteristic “dive-bomber” sounds.

2. Associated Complications:

  • Echocardiogram: To assess cardiac involvement (e.g. cardiomyopathy or conduction defects).
  • 12-lead ECG: Look for conduction abnormalities such as AV block or arrhythmias.
  • Glucose Tolerance Test: To screen for diabetes.
  • Slit Lamp Examination: For cataracts.
  • Pulmonary Function Tests: Assess respiratory muscle involvement.

How would you manage this patient?

1. Symptom Control:

  • Myotonia: Sodium channel blockers such as mexiletine or phenytoin.
  • Weakness: Physiotherapy and orthotic devices for distal muscle weakness (e.g. foot drop splints).
  • Pain: Neuropathic pain agents like gabapentin or amitriptyline.
  • MDT involvement: including physiotherapy, occupational therapy, orthoptist, psychologist.

2. Systemic Complications:

  • Cardiac: Regular monitoring with ECG and echocardiography; pacemaker insertion if conduction defects are present.
  • Respiratory: Non-invasive ventilation for hypoventilation or obstructive sleep apnoea.
  • Diabetes: Optimise glycaemic control with diet or medication.

3. Genetic Counselling:

  • Essential for affected individuals and their families, as the condition is autosomal dominant with anticipation.
  • Prenatal testing is available for families wishing to avoid passing on the condition.

4. Anaesthetic Precautions:

  • Avoid depolarising neuromuscular blockers (e.g. suxamethonium) to prevent worsening myotonia.
  • Be cautious with sedatives and other respiratory depressants.

Viva Questions

1. What are the systemic complications of myotonic dystrophy?

Cardiac arrhythmias, respiratory failure, diabetes, cataracts, testicular atrophy, and gastrointestinal dysmotility.

2. What is the pathophysiology of myotonia in DM1?

Delayed muscle relaxation due to impaired chloride ion channel function caused by misprocessed mRNA from the expanded CTG repeats.

3. What are the risks of general anaesthesia in myotonic dystrophy?

Prolonged recovery, respiratory failure, and increased sensitivity to neuromuscular blocking agents.

4. What is genetic anticipation?

A phenomenon where successive generations experience earlier and more severe manifestations due to increasing trinucleotide repeat expansion.

5. What is the prognosis of myotonic dystrophy?

Progressive disease with a median life expectancy of middle age, often limited by cardiac or respiratory complications.