A five-year-old boy presents with his parents who have concerns about his motor development. He has difficulty climbing stairs – he pulls himself up with the handrails, or goes up sideways. He falls more often than expected for a child his age – and seems to be collapsing rather than tripping. And he gets up from the floor in an awkward way – pushing up on his knees, and kneeling on all fours before getting up.
The GP refers to a paediatrician who sends bloods for creatine kinase estimation. When the result returns grossly elevated at 23570 IU/l she refers him urgently to the tertiary neuromuscular clinic for further assessment and advice.
The boy is seen within two weeks in an urgent clinic with his mother and maternal grandmother. Further history reveals that the family have been concerned about him for a long time, since he was about two years old. His gross motor development was slightly delayed – he sat as expected at six months but never crawled. He bottom shuffled, pulled himself to standing at 15 months and started to walk independently at 18 months. There were no concerns about his fine motor development. He had significant speech and language delay, shows unusual behaviours – lining up objects, getting upset if certain daily routines were not strictly followed – and has persistent temper tantrums. The family are also concerned about the slight broad shape of his head.
Other medical history is unremarkable, as is full system enquiry – apart from longstanding constipation for which he is taking lactulose.
Duchenne muscular dystrophy:
- Is the most common life-limiting inherited muscular dystrophy in the UK.
- Is a multisystem disease that affects skeletal muscle, cardiac muscle, brain, gut and bladder.
- Is X-linked – symptomatic female carriers can present very rarely. About 30% of newly diagnosed patients have either got a spontaneous mutation or their mother is a carrier of the mutation.
- Is the second most common inherited disease, after cystic fibrosis.
- Affects about one in 3,600 – 6,000 boys.
- Is caused by mutations in the dystrophin gene – absent or severely depleted dystrophin leads to a loss of integrity of muscle cells with subsequent destruction that can not be overcome by the muscle repair mechanisms.
- Has a median predicted survival in the UK of mid to late twenties. Quality of life and life expectancy have significantly improved in recent years with improved surveillance treatment.
- Most boys with Duchenne muscular dystrophy present because of concerns about gross motor developmental delay – for example, not walking at 18 months of age, muscle fatigue unusual for their age and significantly reduced walking distance for age. They often don’t have a family history.
- A positive family history usually leads to early screening (creatine kinase with subsequent mutation screening by the clinical genetics service) in newborns.
- Some children present with an incidental finding of elevated alanine transaminase/aspartate aminotransferase with normal bilirubin and gamma-glutamyltransferase and no clinical signs of liver disease. Muscle origin is confirmed by estimation of creatine kinase.
- Some present with speech and language delay, learning difficulties and unusual behaviour but few muscular signs or symptoms.
- More recently, children are referred with mutations detected via microarray genetic testing done for non muscle-related reasons, for example learning difficulties or ADHD.
Screening is done via creatine kinase estimation. This will be very high – initially up to 100 times upper limit of normal. Always confirm elevated values with second sample two weeks apart.
Diagnosis is confirmed by multiplex ligation-dependent probe amplification or, if negative, point mutation screening. Muscle biopsy remains the gold standard for diagnosis. Antenatal diagnosis is possible.
Delayed presentation has become much rarer and might now delay appropriate treatment. Genetic counselling should be provided, and female carriers are at risk of cardiomyopathy – so screening is recommended.
On initial presentation, differentials include:
- Familial delayed gross motor milestones or walking
- Delayed gross motor development following significant illnesses or trauma
- History compatible with motor developmental delay (for example, significant prematurity)
- Significant hypotonia
- Central neurological or genetic problems associated with global developmental delay (for example, association with dysmorphism, delay in all areas of development).
In children with grossly elevated creatine kinase, differential diagnoses include:
- Other dystrophinopathies: intermediate type or Becker’s muscular dystrophy
- Limb-girdle muscular dystrophies
- Congenital muscular dystrophies
- Muscle trauma
- Parainfections, myositis
- Weakness – symmetrical, affecting upper and lower limbs, proximal weakness worse than distal, fatigue, muscle pain and cramps in younger patients, but not as frequently as in Becker’s muscular dystrophy.
- Reduced motor function from two to three years – continuous decline.
- Pseudo hypertrophy of calf- and lower arm muscles, at times generalised.
- Positive Gower’s sign – where the child has to use his hands and arms to ‘walk’ up from a sitting to a standing position because of weak knee and thigh flexors.
- Loss of ambulation at eight to 12 years, later if on steroid treatment.
- Joint contractures – especially ankles, also hips, knees upper limbs and hands
- Nocturnal hypoventilation, weak cough
- Cardiomyopathy (dilated)
- Gut dysmotility
- Death – in late teens to young adulthood because of respiratory or cardiac failure. Life expectancy is significantly improved with respiratory and cardiac support.
Management is with review and follow up in a multidisciplinary neuromuscular clinic. Steroids will be prescribed by the specialist team (there is a risk of adrenal suppression with long-term steroid treatment).
Behavioural problems and learning difficulties will be managed with assessment, advice and appropriate psychological support.
Contractures will be managed with physiotherapy, and possibly surgical release of Achilles tendon. Scoliosis may require corrective surgery.
For patients with swallowing difficulties, food may need to be modified to a consistency that is easier to swallow. For those with respiratory weakness, physiotherapy assessment and support may help, as may swimming. Prophylactic or early antibiotics may be considered and pneumococcal and influenza vaccination will be given.
Those with cardiomyopathy will be managed with ACE inhibitors, B-blockers or diuretics. And those with gut dysmotility may require laxatives, gastrostomy or rectal washouts.
Because Duchenne muscular dystrophy is a life-limiting disease, patients and their families will need psychological support and advice on advanced care planning, including end of life planning.
Dr Stefan Spinty is a consultant paediatric neurologist, and lead consultant for neuromuscular diseases, at Alder Hey Children’s NHS Foundation Trust, Liverpool
Bushby K, Finkel R, Birnkrant DJ, et al.Diagnosis and management of Duchenne muscular dystrophy, part 1: Diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan;9(1):77-93
Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010:9:177-89 Muscular Dystrophy Campaign ; www.muscular-dystrophy.org/