Duchenne Muscular Dystrophy - Pediatrics

Introduction

Disorder of worsening neurologic dysfunction characterized by progressive muscle weakness
- caused by absent dystrophin protein
Epidemiology
- demographics
  - prevalence is 2-3/10,000
  - affects young males only
  - age of onset is between 2-6 years of age
Pathophysiology
- dystrophin absence leads to
  - poor muscle fiber regeneration
  - progressive replacement of muscle tissue with fibrous and fatty tissue
- skeletal and cardiac muscle lose elasticity and strength
Genetics
- X-linked recessive
- Xp21.2 dystrophin gene defect due to point deletion and nonsense mutation
- one third of cases result from spontaneous mutations
Associated conditions
- orthopaedic manifestations
  - calf pseudohypertrophy
  - scoliosis
  - equinovarus foot deformity
  - joint contractures
- nonorthopaedic conditions
  - cardiomyopathy
  - static encephalopathy
- Becker's Muscular Dystrophy
  - similar to Duchenne's in that
    - it is sex-linked recessive
    - calf pseudohypertrophy is present
    - CPK is elevated
  - differs from Duchenne's in that
    - dystrophin protein is decreased instead of absent
    - later onset with slower progression and longer life expectancy (average diagnosis occurs at age 8 compared to 2 years of age with Duchenne's)
    - more prone to cardiomyopathy
Prognosis
- most are unable to ambulate independently by age 10
- most are wheelchair dependent by age 15
- most die of cardiorespiratory problems by age 20

Physical Exam

Symptoms
- progressive weakness affecting proximal muscles first (begins with gluteal muscle weakness)
- gait abnormalities
  - delayed walking
  - toe walking
  - clumsy, waddling gait
  - difficulty climbing stairs, hopping, or jumping
- decreased motor skills
Physical exam
- calf pseudohypertrophy (infiltration of normal muscle with connective tissue)
- deep tendon reflexes present (unlike spinal muscular atrophy)
- lumbar lordosis
  - compensates for gluteal weakness
- Gower's sign
  - rises by walking hands up legs to compensate for gluteus maximus and quadriceps weakness
- Trendelenburg sign

Evaluation

Labs
- markedly elevated CPK levels (10-200x normal)
  - CPK leaks across defective cell membrane
Muscle biopsy
- will show connective tissue infiltration and foci of necrosis
- will show absent dystrophin with staining
DNA testing
- shows absent dystrophin protein
EMG
- myopathic
  - decreased amplitude, short duration, polyphasic motor

Differential Diagnosis

	Similar traits to Duchenne's	Distinguishing traits from Duchenne's
Becker's	• calf pseudohypertrophy • markedly elevated CPK • x-linked transmission	• Becker's has slower progression of weakness with diagnosis made later (~8 yrs) • prone to cardiomyopathy
Spinal muscular atrophy	• proximal weakness	• onset of weakness is earlier in childhood • absent deep tendon reflexes and fasciculations • CPK levels are normal • pseudohypertrophy is absent
Emery-Dreifuss dystrophy	• similar clinical picture	• no calf pseudohypertrophy • CPK levels near normal • elbow and ankle contractures develop early
Limb girdle dystrophy	• progressive motor weakness	• no calf pseudohypertrophy • CPK levels are only mildly elevated
Guillain-Barre syndrome	• acute onset of weakness	• absent deep tendon reflexes • CPK levels are normal

Treatment

Nonoperative
- corticosteroid therapy (prednisone 0.75 mg/kg/day)
  - indications
    - 5 to 7-year-old child with progressive disease
  - goals
    - to maintain ambulatory capacity as long as possible
  - outcomes
    - significant positive effect on disease progression
      - acutely improves strength, slows progressive weakening, prevents scoliosis formation, and prolongs ambulation
      - delays deterioration of pulmonary function
  - side effects
    - osteonecrosis
    - weight gain
    - cushingoid appearance
    - GI symptoms
    - mood lability
    - headaches
    - short stature
    - cataracts
- pulmonary care with nightly ventilation
- rehabilitation
  - techniques
    - physical therapy for range of motion exercises
    - adaptive equipment
    - power wheelchairs
    - KAFO bracing (controversial)
Operative
- soft tissue releases to prolong ambulation
  - indications
    - ambulatory child with Duchenne's
  - techniques
    - hip abduction contractures treated by release of iliotibial band
    - Hip flexion contractures treated by release of sartorius, rectus femoris, and tensor fascia lata
    - hamstring releases
    - Achilles tendon and posterior tibialis lengthenings
  - postoperative care
    - early mobilization and ambulation to prevent deconditioning
- scoliosis surgery (see below)

Scoliosis

Introduction
- considered a neurogenic curve
- occurs in 95% of patients after becoming wheelchair dependent
- curve progresses rapidly from age 13 to 14 years
  - begins with mild hyperlordosis
  - progresses with general kyphosis and scoliosis with varying degrees of pelvic obliquity
  - progresses 1° to 2° per month starting at age 8 to 10 years
- patients may become bedridden by age 16
- treatment is complicated by restrictive pulmonary disease (significant decrease in forced vital capacity)
- cardiac and pulmonary function studies should be obtained pre-operatively as significant declines in function of both organ systems may make spinal fusion too high-risk
Treatment
- nonoperative
  - bracing is contraindicated
    - may interfere with respiration
- operative
  - early PSF with instrumentation
    - indications
      - curve 20-30° in nonambulatory patient
        
        treat early before pulmonary function declines
        
        can wait longer ~ 40° if responding well to corticosteroids
      - FVC drops ≤ 35%
      - rapidly progressive curve
  - PSF with instrumentation to pelvis
    - indications
      - curves ≥ 40°
      - pelvic obliquity ≥ 10°
      - lumbar curve where apex is lower than L1
    - complications
      - malignant hyperthermia is common intraoperatively
        
        pretreat with dantrolene
      - intraoperative cardiac events
  - anterior and posterior spinal fusion
    - indications
      - rarely for stiff curves

Equinovarus Foot

Introduction
- common foot deformity seen with Duchenne muscular dystrophy
Pathoanatomy
- muscle imbalance secondary to muscle replacement with fibrofatty tissue
Diagnosis
- made upon clinical exam
Treatment
- nonoperative
  - stretching, physical therapy, and night time AFO use
- operative
  - Tendinoachilles lengthening with posterior tibialis tendon transfer, toe flexor tenotomies