Myotonic Dystrophy

Overview – Myotonic Dystrophy

Myotonic dystrophy is the most common form of adult-onset muscular dystrophy and is caused by a trinucleotide repeat expansion in the DMPK gene. It leads to abnormal messenger RNA (mRNA) processing, affecting protein synthesis and cellular function in multiple tissues. This multisystem disorder is characterised by progressive muscle weakness, myotonia (difficulty relaxing muscles), and systemic involvement including cardiac, ocular, endocrine, and central nervous system complications.

Definition

• Myotonic dystrophy is a genetic condition that causes progressive muscle wasting and weakness, along with myotonia (delayed muscle relaxation).
• It involves multisystemic effects beyond skeletal muscle, including cardiac conduction defects, cataracts, and endocrine dysfunction.

Aetiology

• Caused by a CTG trinucleotide repeat expansion in the DMPK gene on chromosome 19.
• Inherited in an autosomal dominant fashion.
• Anticipation is observed: repeat size may increase in successive generations, resulting in earlier and more severe disease.

Pathogenesis

• The mutated DMPK gene produces an abnormal mRNA transcript.
• This mRNA accumulates within cells, forming toxic nuclear foci that sequester RNA-binding proteins.
• → Disruption of normal mRNA splicing across various tissues
• → Leads to cellular dysfunction in muscle, heart, eyes, endocrine glands, and CNS

Clinical Features

• Two types:
  • Myotonic Dystrophy Type 1 (DM1) – more severe, with distal muscle weakness
  • Myotonic Dystrophy Type 2 (DM2) – typically milder, with proximal muscle involvement
• Usually presents in 20s–30s
• Key features:
  • Myotonia – delayed muscle relaxation after contraction
  • Progressive muscle weakness, stiffness, tightness, and wasting
  • Facial muscle involvement → ptosis, “hatchet face” appearance
  • Cardiac arrhythmias
  • Cataracts
  • Hypogonadism, insulin resistance
  • Daytime somnolence and cognitive changes

Diagnosis

• Primarily clinical: based on characteristic features and family history
• Confirmatory tests:
  • Genetic testing – detection of CTG repeat expansion
  • Electromyography (EMG) – shows characteristic myotonic discharges
  • Additional assessments: ECG, echocardiography, eye exams

Management

• No cure; management is symptom-directed and multidisciplinary
• Physiotherapy for mobility and function
• Pain management
• Cardiac monitoring and pacemaker if needed
• Ophthalmological care for cataracts
• Endocrine support for insulin resistance or hormonal issues
• Genetic counselling for affected families

Prognosis

• Progressive disorder with variable severity
• Life expectancy is reduced, largely depending on type and systemic involvement
• Most common causes of death: cardiac conduction defects and respiratory failure

Summary – Myotonic Dystrophy

Myotonic dystrophy is an autosomal dominant disorder caused by CTG repeat expansion in the DMPK gene. It presents in early adulthood with progressive muscle weakness, stiffness, and myotonia, and may affect multiple organ systems. Severity and prognosis vary, but cardiac and respiratory complications are the leading causes of mortality. For a broader context, see our Genetics & Cancer Overview page.