Duchenne Muscular Dystrophy

Definition: Duchenne Muscular Dystrophy (DMD) is a severe X-linked recessive disorder caused by mutations in the dystrophin gene (Xp21). It results in absent dystrophin protein, leading to progressive muscle degeneration.

Epidemiology:

• Incidence: ~1 in 3500-5000 male births.
• Inheritance: X-linked recessive. Males affected. Females are carriers.
• New Mutations: ~1/3 are sporadic (new mutation).

Natural History:

• Age 3-5: Symptom onset (delayed walking, difficulty climbing stairs).
• Age 5-10: Progressive weakness. Gowers' sign. Toe walking.
• Age 10-12: Loss of ambulation. Wheelchair-bound.
• Age 15+: Scoliosis progression. Respiratory decline. Cardiomyopathy.
• Age 20-30: Death (usually respiratory or cardiac failure).

Genetics:

• Gene: Dystrophin (DMD gene) on Xp21.
• Mutation Types: Deletions (60%), Duplications (5-10%), Point mutations (30%).
• Result: Complete absence of dystrophin protein.

Pathophysiology:

• Dystrophin: Links cytoskeleton to ECM. Stabilizes sarcolemma during contraction.
• Absence: Membrane fragility. Increased calcium influx. Muscle fiber necrosis.
• Progression: Repeated cycles of necrosis and regeneration. Eventually, fibrosis and fatty replacement.
• CK Elevation: Leakage from damaged muscle fibers.

Becker Muscular Dystrophy (BMD):

• Same gene, but in-frame mutations that allow partial dystrophin function.
• Milder phenotype. Later onset. Longer survival.

Why weakness becomes deformity: The orthopaedic burden of DMD is a direct downstream consequence of progressive, asymmetric muscle weakness acting across growing joints and a growing spine.

• Contractures: Antigravity muscles (gastrocnemius-soleus, hip flexors, iliotibial band) retain relative strength longer than their antagonists (tibialis anterior, hip extensors). The resulting muscle imbalance, combined with prolonged sitting once ambulation is lost, drives fixed equinus, hip flexion contracture and ITB tightness.
• Equinus gait compensation: While still ambulant, boys adopt toe-walking and a lordotic, wide-based stance to keep the ground-reaction force anterior to the knee and posterior to the hip, stabilising both joints despite quadriceps and gluteal weakness. Aggressive Achilles lengthening that destroys this equinus "lock" can precipitate loss of ambulation.
• Neuromuscular scoliosis: Once truncal and paraspinal muscles can no longer balance the seated spine, a long C-shaped collapsing curve with pelvic obliquity develops. Unlike idiopathic scoliosis, it progresses even after skeletal maturity and through the wheelchair years.
• Fragility bone: Disuse osteoporosis (immobility) plus glucocorticoid-induced bone loss produces a fracture-prone skeleton. Vertebral compression fractures and low-energy long-bone fractures (especially distal femur) are common; a femoral fracture in a marginal ambulator frequently ends walking permanently.

DMD is staged by functional ambulatory status, which drives the timing of every orthopaedic decision. The Brooke (upper limb) and Vignos (lower limb) scales remain the classic clinical grading tools.

History:

• Developmental: Delayed walking (18+ months). Difficulty running, climbing, jumping.
• Family History: X-linked pattern. Carrier mother. Affected uncles/brothers.

Physical Examination:

• Gowers' Sign: Uses hands on thighs to stand from floor (proximal weakness).
• Pseudohypertrophy: Calves appear large (fibrofatty replacement).
• Lordosis: Lumbar hyperlordosis (weak hip extensors).
• Toe Walking: Equinus contracture.
• Shoulder Weakness: Weak scapular fixators ('winging').
• Contractures: Equinus, Hip flexion, Iliotibial band.
• Scoliosis: After loss of ambulation.

Orthopaedic Manifestations:

1. Contractures: Equinus (most common), Hip flexion, ITB tightness.
2. Scoliosis: Progressive neuromuscular scoliosis after wheelchair.
3. Fractures: Fragility fractures (osteoporosis from steroids + immobility).

The classic triad of a young boy with proximal weakness, a positive Gowers' sign and a markedly raised CK has a focused differential. Distinguishing features are exam favourites.

Diagnosis:

1. Serum CK: Massively elevated (10-100x normal). Screening test.
2. Genetic Testing: Confirms mutation. Multiplex PCR, MLPA, Sequencing.
3. Muscle Biopsy: Absent dystrophin on immunohistochemistry. Now less used (genetic testing is gold standard).

Orthopaedic Assessment:

1. Spine X-ray: AP and Lateral for scoliosis. Measure Cobb angle.
2. Whole Spine MRI: If planning fusion.
3. Pulmonary Function (FVC): Essential before scoliosis surgery.
4. Cardiac Assessment: Echo, ECG. Cardiomyopathy is universal.
5. DEXA: Bone density assessment.

Natural History:

• Scoliosis develops in nearly 100% of DMD patients after loss of ambulation.
• Progression is rapid (~15-20 degrees/year).

Indications for Spinal Fusion:

• Cobb angle greater than 20-30 degrees AND progressing.
• FVC greater than 35% (some say greater than 30%) - Below this, perioperative risk is very high.

Surgical Technique:

• Posterior Spinal Fusion (PSF): T2/T3 to Pelvis (Iliac or S1 Alar-Iliac screws).
• Instrumentation: Segmental pedicle screws.
• No Anterior Release: Usually not needed.

Perioperative Considerations:

• Anesthesia: TIVA (Total Intravenous Anesthesia). Avoid succinylcholine and volatiles (MH risk).
• Blood Loss: Expect significant. Cell salvage, Tranexamic acid.
• ICU: Often require post-op ICU. May need prolonged NIV.

Outcomes:

• Halts scoliosis progression.
• Maintains sitting balance.
• May improve respiratory function or slow decline.

After Spinal Fusion:

• ICU admission (often 24-48 hours).
• NIV if respiratory compromise.
• Early mobilization to wheelchair (Day 2-3).
• Wound care.
• No brace required (rigid instrumentation).

After Achilles Lengthening:

• Cast 4-6 weeks.
• AFOs after cast removal.
• Intensive physiotherapy.

• With Modern Care: Life expectancy now 20-30 years (previously teens).
• Steroids: Prolong ambulation ~2 years. Delay scoliosis.
• Spinal Fusion: Halts scoliosis progression. Maintains sitting posture. May improve QOL.

• Glucocorticoid regimen: The FOR-DMD randomised trial showed daily prednisone and daily deflazacort both outperform the 10-days-on/10-days-off intermittent regimen, with no significant difference between the two daily drugs. Deflazacort causes less weight gain and fewer behavioural effects but worse growth and more cataracts. Vamorolone (a dissociative steroid) is an emerging alternative with a potentially better bone/growth profile. The "best" regimen remains individualised.
• Should the pelvis always be fused? Long constructs to the pelvis control pelvic obliquity but increase operative time, blood loss and implant prominence. Some series of early, limited instrumentation in low curves (correcting before pelvic obliquity is fixed) report good seating with shorter, lower-morbidity surgery. Threshold of pelvic obliquity at which pelvic fixation becomes mandatory is debated.
• Has steroid use changed the scoliosis equation? Daily glucocorticoids dramatically reduce the incidence and severity of scoliosis, so far fewer steroid-treated boys now require spinal fusion than in the pre-steroid era. The classic teaching of near-universal, rapidly progressive scoliosis largely predates routine daily steroids.
• Are volatile anaesthetics absolutely contraindicated? Succinylcholine is unequivocally contraindicated (hyperkalaemic arrest). The risk from modern volatile agents (rhabdomyolysis/hyperkalaemia) is real but lower; many centres still use total intravenous anaesthesia as the safest default, while acknowledging the volatile-agent recommendation is less absolute.
• Disease-modifying genetic therapy: Exon-skipping antisense oligonucleotides (eteplirsen for exon 51-amenable mutations and related agents) and micro-dystrophin gene therapy (delandistrogene moxeparvovec) are approved in some regions but produce only partial dystrophin restoration; durable functional benefit, cost and access remain uncertain. They supplement, not replace, multidisciplinary musculoskeletal care.

Global epidemiology:

• Birth incidence approximately 1 in 3,500-5,000 live male births; one of the most common lethal childhood genetic disorders worldwide.
• Roughly one-third of cases arise from de novo mutations with no family history.
• With contemporary multidisciplinary care (daily steroids, cardiac and respiratory support, spinal surgery), median survival has risen from the teens into the late 20s-30s.

Side-by-side guidance:

Registry & natural-history data:

• National and international DMD registries (e.g. TREAT-NMD network, the UK NorthStar database, US MD STARnet surveillance) track ambulation, scoliosis surgery rates, cardiac and respiratory milestones and feed trial recruitment.
• Registry data document the falling incidence of spinal fusion in the daily-steroid era and the rising age at loss of ambulation.

High- vs limited-resource practice variation:

• Well-resourced settings: genetic confirmation, daily steroids, non-invasive ventilation, cardiac pharmacotherapy, posterior spinal fusion with segmental instrumentation, and access (variably) to exon-skipping or gene therapy.
• Limited-resource settings: diagnosis may rely on CK and clinical phenotype with limited genetic testing; steroids and bracing remain the mainstay; ventilatory and spinal-surgery access may be constrained, shifting emphasis toward seating, contracture prevention and palliative goals.