Medicine – Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive X-linked recessive muscular dystrophy caused by pathogenic variants in the DMD gene, resulting in an almost complete absence of functional dystrophin protein.

Because dystrophin is essential for maintaining the structural stability of muscle fibres during contraction, its absence leads to repeated muscle-fibre injury, degeneration, and replacement by fat and connective tissue.

1. Inheritance

DMD is inherited in an X-linked recessive pattern.

It therefore predominantly affects boys, while females are usually carriers.

Some female carriers can develop mild muscle weakness or cardiomyopathy because of skewed X-chromosome inactivation.

2. Dystrophin Deficiency

The DMD gene encodes dystrophin, a structural protein that links the muscle-cell cytoskeleton to the surrounding extracellular matrix.

In Duchenne muscular dystrophy, functional dystrophin is essentially absent.

This makes the muscle membrane fragile during contraction and results in progressive muscle-cell damage.

3. Comparison with Becker Muscular Dystrophy

Duchenne and Becker muscular dystrophy are caused by mutations in the same gene.

The key difference is:

Duchenne muscular dystrophy → dystrophin absent or nearly absent.

Becker muscular dystrophy → dystrophin reduced or structurally abnormal but partly functional.

As a result, Duchenne disease presents earlier and is more severe.

4. Age of Presentation

Symptoms usually become apparent in early childhood, often between about 2 and 5 years of age.

Parents may notice delayed motor milestones, frequent falls, difficulty running, or difficulty climbing stairs.

5. Girdle Muscle Weakness

The weakness is predominantly proximal, especially affecting the pelvic-girdle muscles.

Children may have difficulty:

Running.

Jumping.

Climbing stairs.

Getting up from the floor.

Keeping up with other children.

As weakness progresses, the shoulder-girdle muscles also become affected.

6. Waddling Gait

Weakness of the hip abductor and pelvic-girdle muscles causes a characteristic waddling gait.

The child shifts the trunk from side to side while walking to compensate for weak hip muscles.

Lumbar lordosis may also become more pronounced.

7. Gowers Sign

A classic clinical finding is Gowers sign.

When rising from the floor, the child uses the hands to push on the knees and then “climbs” up the thighs.

This occurs because the hip and thigh muscles are too weak to raise the body efficiently without assistance from the upper limbs.

Therefore:

Gowers sign = proximal pelvic-girdle weakness.

8. Calf Pseudohypertrophy

The calf muscles may appear unusually large.

This is called calf pseudohypertrophy.

The enlargement is not caused by increased functional muscle tissue. Instead, damaged muscle fibres are progressively replaced by fat and connective tissue.

Thus:

Large calves + weak child → think Duchenne muscular dystrophy.

9. Raised Creatine Kinase

Serum creatine kinase (CK) is typically markedly elevated, often many times above the normal range.

CK leaks from damaged muscle fibres into the blood.

The CK may be very high even before severe weakness becomes obvious.

10. Other Laboratory Findings

Other muscle-derived enzymes may also be elevated, including:

AST.

ALT.

This is important because elevated transaminases in a child with muscle weakness may be mistakenly interpreted as primary liver disease.

A markedly elevated CK points toward skeletal-muscle injury.

11. Loss of Walking Ability

Without effective modern disease-modifying management, boys with classic DMD historically lost independent walking ability around the early teenage years, often near 12 years of age.

However, this older figure is no longer absolute.

Modern corticosteroid therapy, rehabilitation, cardiac care, respiratory support, and newer targeted treatments can prolong ambulation and survival.

12. Contractures

As muscle weakness progresses, patients may develop joint contractures.

Common sites include:

Ankles.

Knees.

Hips.

Tightness of the Achilles tendons may contribute to toe walking.

Regular stretching and physiotherapy are important to delay contracture formation.

13. Scoliosis

Loss of trunk muscle strength can lead to scoliosis, particularly after loss of independent ambulation.

Severe scoliosis can further impair respiratory mechanics.

Postural management and orthopaedic assessment are therefore important.

14. Respiratory Muscle Weakness

Progressive weakness eventually affects the respiratory muscles.

This can cause:

Weak cough.

Poor secretion clearance.

Recurrent chest infections.

Nocturnal hypoventilation.

Progressive respiratory failure.

Respiratory complications were historically a major cause of death.

15. Cardiac Involvement

Dystrophin is also important in cardiac muscle.

Patients commonly develop dilated cardiomyopathy.

They may also develop:

Left ventricular dysfunction.

Cardiac fibrosis.

Arrhythmias.

Cardiac disease may progress even when skeletal-muscle symptoms dominate clinically.

16. Cardiac Monitoring

Regular cardiac surveillance is therefore essential.

This may include:

ECG.

Echocardiography.

Cardiac MRI.

Early treatment of cardiomyopathy can improve long-term outcomes.

17. Cognitive and Neurodevelopmental Features

Dystrophin is also expressed in the brain.

Some boys with DMD may have:

Learning difficulties.

Attention problems.

Autism-spectrum features.

Speech or language delay.

Intellectual ability varies widely, and severe cognitive impairment is not universal.

18. Diagnosis

Diagnosis is usually established by:

Clinical features.

Very high serum CK.

Genetic testing for pathogenic variants in the DMD gene.

Genetic confirmation is important because it establishes the diagnosis and may determine eligibility for mutation-specific therapies.

19. Muscle Biopsy

Muscle biopsy is now less commonly required when genetic testing confirms the diagnosis.

When performed, it may demonstrate severe dystrophic changes and absence of dystrophin on immunostaining.

20. Genetic Counselling

Because DMD is X-linked, genetic counselling is important.

Carrier testing may be offered to appropriate female relatives.

Carrier women may also require cardiac surveillance because they can develop cardiomyopathy even without significant skeletal-muscle weakness.

21. Corticosteroid Therapy

Corticosteroids such as prednisolone or deflazacort have long been used to slow the decline in muscle strength.

They can help:

Prolong walking ability.

Preserve upper-limb function.

Delay scoliosis.

Support respiratory function.

Treatment requires monitoring for long-term adverse effects.

22. Modern Disease-Modifying Therapy

Management has expanded beyond supportive care.

Selected patients may be eligible for mutation-specific treatments, including exon-skipping therapies or other targeted approaches, depending on the exact DMD gene variant and local regulatory approval.

Gene-based treatments are also an evolving area of DMD management.

23. Respiratory Management

Respiratory care includes:

Regular pulmonary-function assessment.

Airway-clearance techniques.

Assisted cough when needed.

Non-invasive ventilation for nocturnal hypoventilation or respiratory failure.

These interventions have substantially improved survival.

24. Cardiac Treatment

Cardiomyopathy may be treated with standard cardiac therapies.

These can include:

ACE inhibitors or ARBs.

Beta-blockers.

Mineralocorticoid-receptor antagonists in appropriate patients.

Early cardiac treatment is an important part of modern DMD care.

25. Prognosis

The older statement that patients generally die from respiratory or cardiac failure in their 20s or early 30s reflects historical experience.

With modern multidisciplinary care, many patients now survive well into adulthood, and survival continues to improve.

The major long-term threats remain:

Cardiomyopathy.

Respiratory failure.

But both can now be monitored and treated much more effectively than in the past.

26. Duchenne Muscular Dystrophy – Note Form

Inheritance: X-linked recessive.

Gene: DMD gene.

Protein abnormality: functional dystrophin essentially absent.

Onset: early childhood.

Weakness: progressive proximal pelvic- and shoulder-girdle weakness.

Gait: waddling gait.

Gowers sign: uses hands to climb up the legs when standing from the floor.

Calves: pseudohypertrophy due to fat and connective-tissue replacement.

CK: markedly raised.

Mobility: walking ability is progressively lost, historically around early adolescence, but modern treatment may prolong ambulation.

Respiratory complication: progressive respiratory muscle weakness and respiratory failure.

Cardiac complication: dilated cardiomyopathy and arrhythmias.

Diagnosis: high CK + DMD genetic testing.

Management: corticosteroids, physiotherapy, cardiac surveillance, respiratory support, genetic counselling, and selected mutation-specific therapies.

Key Clinical Pattern

Remember DMD as:

Young boy + proximal muscle weakness + waddling gait + Gowers sign + calf pseudohypertrophy + very high CK.

The core molecular defect is:

X-linked DMD mutation → absent dystrophin.

The easiest comparison with Becker muscular dystrophy is:

Duchenne → absent dystrophin → early onset + severe disease.

Becker → some dystrophin remains → later onset + milder disease.