🧠 Duchenne Muscular Dystrophy (DMD)

1. Definition

Duchenne Muscular Dystrophy (DMD) is a progressive, X-linked recessive neuromuscular disorder caused by mutations in the dystrophin gene, leading to absence of functional dystrophin protein.
It primarily affects boys and leads to progressive muscle weakness, loss of ambulation, and eventually cardiopulmonary complications.

2. Causes

Genetic mutation in the DMD gene on the X chromosome (Xp21.2)
Mutation leads to absence of dystrophin, a structural protein in muscle fibers
~70% due to large deletions/duplications, ~30% due to point mutations or small indels

3. Risk Factors

Family history of DMD (X-linked inheritance)
Carrier mother (can be asymptomatic)
Male sex (due to X-linked pattern)

4. Types

Type	Features
Duchenne	Early onset (<5 years), rapid progression, no dystrophin
Becker	Later onset, slower progression, partial dystrophin

5. Pathogenesis

Dystrophin links the cytoskeleton of muscle cells to the extracellular matrix
Absence leads to:
- Muscle membrane fragility
- Calcium influx → inflammation
- Fibrosis and fatty infiltration
Affects skeletal, cardiac, and respiratory muscles

6. Clinical Presentation

Symptoms

Delayed walking (>18 months)
Difficulty climbing stairs, frequent falls
Waddling gait, toe-walking
Gower’s sign

Signs

Pseudohypertrophy of calves
Lumbar lordosis
Proximal muscle weakness
Loss of ambulation (~age 12)

Physical Examination Findings

Decreased reflexes (later stages)
Scoliosis
Contractures
Poor head control in infants

7. Organ & System Complications

System	Complications
Musculoskeletal	Contractures, scoliosis, wheelchair dependency
Cardiac	Dilated cardiomyopathy, arrhythmias
Respiratory	Hypoventilation, pneumonia, sleep apnea
Gastrointestinal	Dysphagia, constipation
Neurological	Mild cognitive impairment
Psychosocial	Anxiety, depression, learning difficulties

8. Diagnostic Investigations

Test	Purpose
Creatine Kinase (CK)	Very high (>10,000 IU/L)
Genetic Testing	MLPA (Multiplex Ligation-dependent Probe Amplification) or PCR to identify DMD gene mutations
Muscle Biopsy	Shows absence of dystrophin (if needed)
EMG	Myopathic pattern

9. Other Relevant Investigations

Investigation	Purpose
Echocardiogram / ECG	Baseline and annual screening
Pulmonary function test	Annually from age 6–7
Sleep study	Assess for nocturnal hypoventilation
Neuropsych assessment	If learning difficulties suspected
Maternal carrier testing	For genetic counseling

10. Treatment

Curative/Definitive

No current cure; gene therapy is under investigation

Empirical

Corticosteroids (prednisolone or deflazacort) to slow the disease progression

Supportive

Physiotherapy, orthoses, wheelchair planning
Cardiac care: ACE inhibitors, beta-blockers
Respiratory care: NIV (e.g. BIPAP), cough-assist devices
Nutritional support, speech and swallowing therapy

Palliative

Symptom management and end-of-life care for advanced disease

11. Long-Term Medications Side Effects

Medication	Side Effects	Monitoring Tests	Expected Findings
Prednisolone	Cushingoid features, growth suppression, osteoporosis	Growth chart, BP, DEXA, glucose	Short stature, ↑ glucose, ↓ BMD
Deflazacort	Similar to prednisolone, less weight gain	Same as above	Similar
ACE inhibitors	Hypotension, hyperkalemia	BP, renal function, potassium	Monitor creatinine, K+

12. Surveillance for the Disease

Domain	Frequency	What to Monitor
Cardiac	Annually	Echo, ECG
Respiratory	Yearly from age 6–7	Spirometry, sleep study
Musculoskeletal	Every 6–12 months	Contractures, scoliosis
Growth/Nutrition	Every visit	Weight, height, BMI
Bone Health	Every 1–2 years if on steroids	DEXA scan
Cognitive/Psych	As needed	Learning evaluation, emotional wellbeing

13. Malaysia Support Group for Parents

Support Group	Description	Contact/Link
Malaysia Rare Disorders Society (MRDS)	Parent support for rare conditions including DMD	MRDS Facebook
Persatuan Penyakit Jarang Jumpa Malaysia	National rare disease advocacy	rare.org.my
Parent Support (Hospital KL & USM)	Peer support via hospital-based clinics	Ask neurologist/genetic counselor