• Clinical science

Spinal muscular atrophy


Spinal muscular atrophy (SMA) refers to a group of autosomal recessive motor neuron diseases that are caused by apoptosis of lower motor neurons. Patients typically present during infancy or early childhood with progressive weakness, hypotonia, muscle atrophy, hyporeflexia/areflexia, and varying degrees of bulbar weakness. The severity of disease is related to the age of onset; type 1 SMA (Werdnig-Hoffman disease) is associated with death within the first two years of life as a result of respiratory muscle paralysis or aspiration pneumonia. With other types of SMA, children usually survive to adulthood, but motor milestones may be delayed and joint contractures and/or deformities of the spine can occur. The diagnosis is confirmed by genetic testing. In 2016, the FDA approved the use of nusinersen, which is highly effective in halting the progression of SMA; in 2019, onasemnogene abeparvovec, a potentially curative genetic therapy, was approved. Supportive therapy is aimed at preventing respiratory and orthopedic complications.


  • Incidence: 4–10 per 100,000 live births
  • Sex: >


Epidemiological data refers to the US, unless otherwise specified.




  • Congenital motor neuron disease that only involves the lower motor neurons (spinal ± bulbar motor neurons) muscle weakness, hypotonia, bulbar symptom
  • Sensations are not affected
  • Motor neurons of cranial nerves III, IV, and VI, and sacral motor neurons not affected → preserved eye movement and continence


Clinical features

Type of SMA Type I (Werdnig-Hoffman disease) Type II Type III (Kugelberg-Welander disease) Type IV (adult SMA)
Relative frequency
  • 25%
  • 50%
  • 25%
  • 25%
  • Severe
  • Intermediate
  • Mild
  • Mild
Age of onset
  • 0–6 months
  • 7–18 months
  • > 18 months
  • 10–30 years
Typical features
  • Variable degree of muscle weakness
  • Cramps, muscle aches
  • Joint pain
Motor milestones

Never sits or attains head control

Able to sit independently, but cannot stand without support

Able to stand and walk independently

Prognosis Life expectancy (< 2 years) Life expectancy (> 2 years)

Near normal life expectancy

The most common causes of death among patients with SMA are respiratory insufficiency (due to respiratory muscle weakness) and aspiration pneumonia (due to bulbar weakness)!

The older the age of onset, the better the prognosis!

Type Inon-sitters, type II → sitters, type III → walkers



  • Definitive therapy:
    • Nusinersen
      • An antisense nucleotide that alters differential splicing of the transcript of the SMN2 gene so it produces a functional SMN1 protein
      • Requires annual intrathecal injections
    • Onasemnogene abeparvovec
      • An agent based on an adenoviral vector that carries a normal copy of SMN1 to the lower motor neurons of the spinal cord
      • Should be administered intravenously once in a lifetime
  • Supportive therapy
    • Respiratory support
    • Nutritional support
    • Physical rehabilitation
    • Orthotics to prevent joint and spine deformities



  1. Genetic testing: best initial and confirmatory test
  2. Further tests
    • Laboratory tests: normal or mildly elevated creatine kinase
    • EMG: spontaneous, large-amplitude, low-frequency electrical activity (rarified interference pattern)
    • Muscle biopsy: atrophy of groups of motor units interspersed with normal or hypertrophied motor units


Differential diagnoses


The differential diagnoses listed here are not exhaustive.