Myotonic Dystrophy

 

• Background

  Pathophysiology and genetics

  • Autosomal dominant excess of CTG triplet repeats in the 3' untranslated region of the DMPK gene on chromosome 19.
  • Faulty mRNA accumulates in the nucleus and binds to RNA proteins, disrupting transcription. Causes a chloride channelopathy due to altered splicing of muscle-specific chloride channel 1.
  • Maternal transmission is much commoner.

  CTG repeat numbers:

  • 5-37: normal:
  • 38-49: unaffected but risk of transmission to children due to anticipation.
  • ≥50: diagnostic for DM1. Risk of cataracts.
  • ≥200: muscle symptoms.
  • ≥1000: symptoms from birth (congenital DM1).

  Epidemiology

  • Mean onset age 10-30.
  • Commonest adult-onset muscular dystrophy.

  Proximal myotonic myopathy (DM2)

  • Rarer from of myotonic dystrophic, due to ZNF9 mutation.
  • Milder symptoms, which only present in adulthood.

• Signs and symptoms

  • Myotonia: delayed muscle relaxation which means they can't release grip.
  • Muscle wasting → weak distal limbs, ptosis, expressionless face, slurred/indistinct speech.
  • Facial: frontal balding, long/thin face, cataracts.
  • CNS: apathy, hypersomnia, mild intellectual impairment (more severe if earlier onset).
  • Cardiovascular: cardiomyopathy, heart block, insulin resistance.
  • Central and/or obstructive sleep apnoea.
  • Congenital DM1: polyhydramnios, late pregnancy loss, floppy baby, V-shaped upper lip.

• Investigations

  Genetic testing:

  • Can be in symptomatic individuals, pre-symptomatic (predictive testing), or prenatally.
  • DM2 testing if DM1 negative.

  Other investigations – EMG, muscle biopsy – are not needed for diagnosis. CK may be normal or mildly elevated.

  Testing for complications:

  • Annual ECG and cataracts screening.
  • Sleep study if apnoea suspected.

• Management

  • Physiotherapy for weakness and gait problems. Includes strength training and aerobic exercise programmes.
  • If myotonia is significant – not actually the case in many patients – consider TCA (clomipramine or imipramine) or taurine.
  • Some patients may benefit from a pacemaker or ICD.
  • NIV if there is sleep apnoea.

• Prognosis

  Life expectancy is 50 years. Deaths are usually cardiac.