- Clinical science
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. 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.
- Motor neuron disease that only involves the lower motor neurons (spinal ± bulbar motor neurons) → muscle weakness, hypotonia, bulbar symptoms; preserved sensations
- Motor neurons of cranial nerves III, IV, and VI, and sacral motor neurons not affected → preserved eye movement and continence
|Type of SMA||Type I (Werdnig-Hoffman disease)||Type II||Type III (Kugelberg-Welander disease)||Type IV (adult SMA)|
|Age of onset||0–6 months||7–18 months||> 18 months||10–30 years|
|Typical features|| |
|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 older the age of onset, the better the prognosis!
Type I → non-sitters, type II → sitters, type III → walkers
- Genetic testing: best initial and confirmatory test
- Further tests
- Certain viral infections (polio, coxsackievirus, echovirus, West Nile virus) → much more acute onset of flaccid paralysis, ascending paralysis (i.e., starts distally)
- Hypotonic cerebral palsy → non-progressive weakness
- Muscular dystrophies → ↑↑ creatine kinase, characteristic findings on muscle biopsy
- Rare juvenile form of amyotrophic lateral sclerosis → predominantly bulbar weakness with minimal involvement of anterior horn cells
- Motor neuron degeneration associated with severe arthrogryposis
The differential diagnoses listed here are not exhaustive.