Skip to main content
Public beta This website is in public beta – please give your feedback.
Conditions

Duchenne muscular dystrophy

Duchenne muscular dystrophy is a genetic condition that features muscle weakness that worsens much more rapidly than in other muscular dystrophies. Individuals tend to present in early childhood.

Overview

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic condition characterised by progressive muscle degeneration resulting in weakness, loss of motor function, cardiorespiratory complications and variable non-progressive intellectual disability.

Because it is X-linked, the vast majority of DMD patients are boys. The mean age of symptom onset is two to three years.

Clinical features

  • Common presenting features of DMD are:
    • developmental delay or loss of motor milestones;
    • toe-walking;
    • clumsiness;
    • frequent falls; and
    • positive Gower’s sign.
  • As the condition advances, there is progressive muscle weakness and atrophy, as well as pseudohypertrophy of muscle (due to fatty fibrous replacement of muscle), most often noticed in the calves. This results in raised blood creatine kinase levels. Most patients lose ambulation by mid-childhood (the mean age is nine years).
  • Other features of the condition include:
    • non-progressive intellectual disability (in around 30% of patients);
    • progressive scoliosis requiring surgery;
    • impaired feeding, requiring gastrostomy feeding; and
    • cardiac involvement – including:
      • dilated cardiomyopathy;
      • conduction anomalies; and
      • arrhythmias.
  • Progressive muscle weakness eventually results in respiratory failure. Death in early to mid-adulthood is usually due to cardiac or respiratory complications.
  • Female carriers of DMD are usually unaffected, but up to 20% may manifest cardiac involvement.
  • Differential diagnoses of DMD include Becker muscular dystrophy and limb girdle muscular dystrophy.
  • Prevalence of DMD is estimated at between 15 and 20 cases per 100,000 newborns.

Genetics

DMD is caused by genetic variants in the dystrophin gene (DMD), which result in dystrophin protein expression levels of less than 5% of normal. Less damaging genetic variants cause Becker muscular dystrophy, which features higher levels of dystrophin expression and a less severe clinical presentation.

Dystrophin forms part of a complex that anchors actin to the cell membrane, and is important in stabilising the muscle cell membrane. Loss of dystrophin expression results in myofiber loss, resulting in muscle damage and degeneration.

About 60%–65% of cases of DMD are caused by large out-of-frame deletions that remove one or more exons of the DMD gene. Approximately 5% are the result of exon duplication, and the remaining 30%–35% are caused by nonsense or frameshift variants. Becker muscular dystrophy is caused by in-frame genetic variants that result in an abnormal dystrophin protein that nevertheless retains some function, hence the milder phenotype.

Note that where genomic test results are negative for DMD, or where the consequence of a genetic variant cannot be predicted but a high clinical index of suspicion remains, muscle biopsy with staining for dystrophin expression may be useful.

For information about testing, see Presentation: Child with progressive muscle weakness/suspected muscular dystrophy.

Inheritance and genomic counselling

Because DMD is an X-linked recessive condition, the majority of patients are boys. Approximately 50% of cases occur de novo and 50% are inherited from the boy’s mother. It is important to establish whether the mother is a carrier because, if she is, any future male pregnancies have a 50% chance of being affected, and female pregnancies have a 50% chance of being a carrier. In addition, female carriers require cardiac surveillance. For information about carrier testing for DMD, see Presentation: Pregnancy at risk of Duchenne or Becker muscular dystrophy.

Where blood tests do not identify a pathogenic variant in the mother, there remains a 20% chance of a future son being affected (overall probability to a future pregnancy is 5%). This is because of the significant rate of constitutional (germline) mosaicism.

Families should be offered counselling by the local clinical genetics service in advance of future conception. Prenatal and/or pre-implantation genetic diagnosis may be considered. Non-invasive prenatal diagnosis (NIPD) can also be performed for a number of X-linked conditions, including DMD, from approximately eight to nine weeks’ gestation. This will determine the sex of the fetus at an early stage; if it is male, invasive testing may then be offered for the familial pathogenic variant known to cause BMD.

Management

Management of children with DMD is complex and should be delivered via a multidisciplinary team; detailed suggested approaches have been published by several authors. Commonly, care will be led by a paediatric neurologist together with a community paediatrician. Children often require input from the respiratory, cardiac, orthopaedic and endocrine teams, in addition to intensive physiotherapy and occupational therapy input and psychosocial support.

Gene-directed therapies and trials

Antisense oligonucleotide therapies, which induce exon ‘skipping’, are currently undergoing clinical trial. These therapies aim to skip over the genetic variant that results in frame shift, thereby improving dystrophin expression level (albeit of a truncated form of the protein).

Resources

For clinicians

References:

For patients

↑ Back to top
  • Last reviewed: 25/04/2023
  • Next review due: 25/04/2025
  • Authors: Dr Elizabeth Radford
  • Reviewers: Dr Amy Frost, Dr Lianne Gompertz