Duchenne Muscular Dystrophy (DMD)

 

Duchenne Muscular Dystrophy (DMD) — Key Points

Overview

Most common and severe childhood muscular dystrophy

X-linked recessive disorder

Caused by mutation in the DMD gene (Xp21) → absence of dystrophin

Affects mainly boys; females are usually carriers

Pathophysiology

Dystrophin links:

Cytoskeleton (actin) → sarcolemma → extracellular matrix

Absence causes:

Muscle fiber instability

Repeated muscle injury

Inflammation and fibrosis

Progressive muscle weakness

Clinical Features

Onset: 2–5 years

Progressive proximal muscle weakness:

Pelvic girdle > shoulder girdle

Difficulty:

Running

Climbing stairs

Rising from floor

Classic Signs

Gowers sign (using hands to push on thighs to stand)

Calf pseudohypertrophy (fat/fibrosis replacement)

Waddling gait

Frequent falls

Toe walking

Loss of ambulation usually by 10–13 years

Laboratory Findings

Markedly elevated CK (often >10,000 U/L)

Elevated AST/ALT due to muscle injury

Genetic testing confirms diagnosis

Diagnosis

1. Genetic testing

First-line diagnostic test

Detects dystrophin gene deletion/duplication/mutation

2. Muscle biopsy (if genetic testing inconclusive)

Absent/reduced dystrophin staining

Cardiac Involvement

Very common due to dystrophin deficiency in myocardium

Main manifestations:

Dilated cardiomyopathy

Myocardial fibrosis (especially posterolateral LV wall)

Arrhythmias (less common)

Monitoring:

Baseline ECG + echocardiography/cardiac MRI

Regular cardiac surveillance

Treatment:

ACE inhibitors/ARBs

Mineralocorticoid receptor antagonists (e.g., eplerenone)

Heart failure therapy when indicated

Respiratory Complications

Progressive respiratory muscle weakness

Restrictive lung disease

Nocturnal hypoventilation

Risk of respiratory failure

Monitoring:

Pulmonary function tests

Sleep studies when indicated

Treatment

No cure, but progression can be slowed:

1. Corticosteroids

Prednisone

Deflazacort

Improve strength and delay loss of ambulation

2. Mutation-specific therapies

Exon skipping therapies (selected mutations)

Gene therapy approaches (evolving)

3. Supportive care

Physiotherapy and stretching

Orthopedic management

Respiratory support

Cardiac surveillance

Prognosis

Progressive disability

Loss of walking ability in early adolescence

Death commonly due to:

Respiratory failure

Cardiomyopathy/heart failure

High-Yield Exam Points

DMD = X-linked recessive + dystrophin deficiency

Onset before 5 years

Gowers sign + calf pseudohypertrophy

CK is massively elevated

Becker muscular dystrophy = same gene defect but partial dystrophin → milder disease

Cardiac hallmark = dilated cardiomyopathy with myocardial fibrosis