Neurological disease in a child: Myotonic dystrophy Flashcards
Define myotonic dystrophy.
Autosomal dominant multisystem disorder characterised by progressive muscle wasting, muscle weakness and myotonia (abnormal sustained contraction of muscle).
Explain the aetiology/risk factors of myotonic dystrophy.
Genetic defect: Caused by expansion of CTG nucleotide triplet repeats at the 3’UTR of the myotonic dystrophy gene on chromosome 19. This gene codes for DMPK.
Genetic anticipation: The disease has earlier onset or increased severity in the offspring than in parents as a result of further triplet repeat expansion in successive generations.
What is the pathophysiology of myotonic dystrophy?
Pathophysiology: Disturbances in muscle fibre maturation with incomplete differentiation.
Infants: Small undifferentiated muscle fibres.
Children: Type 1 fibre atrophy, central nuclei, sarcoplasmic masses, ring fibres.
Summarise the epidemiology of myotonic dystrophy.
2/10,000 live births (UK). Severe congenital type is much rarer and almost always inherited via the mother.
What does the severity of myotonic dystrophy depend on?
Depends on number of CTG repeats.
- Unaffected individuals (5-27 repeats)
- Mild myotonic dystrophy (50-100 repeats): Cataracts, slight muscle weakness in adulthood.
- Classic myotonic dystrophy (100-1000 repeats): Myotonia, muscle wasting, frontal balding, hypogonadism, cardiomyopathy, cardiac arrhythmias, DM, respiratory impairment, adverse reaction to anaesthesia.
- Congenital myotonic dystrophy (1000-4000 repeats)
What are symptoms of myotonic dystrophy?
At birth: Hypotonia, respiratory and feeding difficulties, marked facial weakness. Myotonia is not a feature of the condition at this stage.
If infants survives: Gradual improvement in muscle strength and tone, delayed motor development, persistence of facial weakness, severe learning disabilities (60-70% of case), classic features of myotonic dystrophy by the age of 10.
What are signs of myotonic dystrophy?
Peripheral weakeness: Hands (unable to release grip), forearms and feet as opposed to proximal weakness (hip, shoulder) in other dystrophies.
Myopathic facies: Facial muscleweakness and wasting; bilateral ptosis, wasting of frontalis and temporalis muscle, and weakness of sternomastoids, all of which result in lack of facial expression.
What are appropriate investigations for myotonic dystrophy?
Blood: CPK may be raised.
Muscle biopsy
EMG: Characteristic ‘diver boomber’ spontaneous electrical discharge by age.
DNA mutation analysis: Sizing of the repeat array by PCR and/or souther blotting.
What is the management for myotonic dystrophy?
Physiotherapy: Strength and flexibility training.
SALT: Difficulties swallowing and dysarthria due to muscle weakness.
Occupational therapy: Specially designed utensils for hand weakness, wrist braces.
Medical: Myotonia may be treated with quinine or procainamide. Support respiratory and GI problems. Monitor for deformities.
Surgical: Cataract operations.
Orthopaedic: Ankle–foot arthroses for foot-drop.
Genetic counselling: For antenatal diagnosis.
Psychological support: For parent and child.
What are complications associated with myotonic dystrophy?
Joint contractures, foot deformities, early-onset dementia.
What is the prognosis of myotonic dystrophy?
Depends on the number of CTG repeats, extent of learning disability and early appropriate multidisciplinary involvement.
The older the child is when muscle weakness is first noticed, the slower the progression and less serious the consequences. Most do not survive past 50 years of age.
