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Updated: Jun 15 2021

Spinal Muscular Atrophy

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  • summary
    • Spinal Muscular Atrophy is a common genetic disease caused by an autosomal recessive mutation in the survival motor neuron gene. The condition presents with progressive motor weakness, scoliosis, hip dislocations, and lower extremity contractures. 
    • Diagnosis is made by DNA analysis and muscle biopsy.
    • Treatment involves a multidisciplinary approach to address motor weakness, scoliosis, and lower extremity contractures. Treatment of associated hip dislocation is observation.
  • Epidemiology
    • Incidence
      • most common genetic disease resulting in death during childhood
      • 1 in 10,000 live births
    • Anatomic location
      • progressive weakness starts proximally and moves distally
  • Etiology
    • Pathophysiology
      • caused by progressive loss of alpha-motor neurons in anterior horn of spinal cord
    • Genetics
      • inheritance
        • autosomal recessive
      • mutation
        • survival motor neuron (SMN) gene mutation
          • present in 90% of cases of SMA
          • a telomeric gene deletion
          • SMN critical to RNA metabolism and is a mediator of apoptosis
          • there are two SMN genes
          • all patients with SMA lack SMN-I protein
          • severity of disease based on number of functional copies of SMN-II
    • Associated conditions
      • orthopaedic manifestations of SMA
        • hip dislocation and subluxation
        • scoliosis
        • lower extremity contractures
  • Classification
      • Types of Spinal Muscle Atrophy
      • Type
      • Name
      • Presentation
      • Prognosis
      • Type I
      • Acute Werdnig-Hoffman disease
      • Present at < 6 months
      • Absent DTR
      • Tongue fasciculations
      • Poor, usually die by 2 yrs.
      • Type II
      • Chronic Werdnig-Hoffman disease
      • Present at 6-12 months
      • Muscle weakness worse in LE
      • Can sit but cant walk
      • May live to 5th decade
      • Type III
      • Kugelberg-Welander disease
      • Present at 2-15 years
      • Proximal weakness
      • Walk as children, wheelchair as adult
      • Normal life expectancy - may need respiratory support
  • Presentation
    • Symptoms
      • symmetric progressive weakness that is
        • more profound in lower-extremity than upper extremity
        • more profound proximally than distally
    • Physical exam
      • absent deep tendon reflexes
        • distinguishes from Duchenne's muscular dystrophy where DTR are present
      • fasciculations present
  • Imaging
    • Radiographs
      • scoliosis series
      • pelvis
  • Evaluation
    • Diagnosis based on
      • DNA analysis
      • muscle biopsy
      • prenatal diagnosis is possible
  • Treatment
    • Nonoperative
      • Nusinersen has been FDA approved for treatment of SMA. It is administered intra-thecally.
    • Operative
      • treat associated orthopaedic disorders (details below)
        • hip dislocation
        • scoliosis
        • lower extremity contractures
  • Hip Dislocation
    • Overview
      • hip subluxation and dislocation occur in 62% with type II SMA, and less frequently in Type III.
    • Treatment
      • nonoperative
        • observation alone (leave dislocated)
          • indications
            • standard of care as dislocations typically remain painless and high recurrence rate if open reduction attempted
  • Scoliosis
    • Overview
      • the development of scoliosis is almost universal
      • usually occurs by age 2 to 3 years
      • often progressive
    • Treatment
      • nonoperative
        • bracing
          • indications
            • devices may delay but not prevent surgery in children younger than ten years
      • operative
        • PSF with fusion to pelvis
          • indications
            • progressive curve
          • technique
            • address hip contractures and any other lower extremity contractures before PSF to ensure seating balance
            • to allow for intrathecal Nusinersen to be given after spine surgery, perfrom a laminectomy in the lower lumbar spine that is kept free of fusion. perform fusion of spine around this laminectomy
          • outcomes
            • for improved wheelchair sitting
            • may lead to temporary loss of upper extremity function
        • Combined PSF with anterior releases/fusion
          • indications
            • curves >100 degrees
            • very young child with high risk of crankshaft phenomenon
          • contraindications
            • pulmonary compromise
          • typically not necessary due to the high flexibility of SMA curves
  • Hip, knee, and ankle contractures
    • Overview
      • Common in the hip and knee
      • Nonambulators also develop ankle equinus
    • Treatment
      • Physical therapy
      • Surgical release is controversial as function in nonwalkers is rarely improved and recurrence is common
    • Prognosis
      • Severity of disease based on number of functional copies of SMN-II
      • Type 1 SMA has the worst prognosis, with majority of patients dying by age 2
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