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.
Epidemiological data refers to the US, unless otherwise specified.
- Autosomal recessive: defect in the SMN1 gene; on chromosome 5q → defect in the assembly of small nuclear ribonucleoprotein (snRNP) to form the SMN complex → apoptosis of lower motor neurons (especially the anterior horn cells in the spinal cord) in the later stages of fetal development and postnatal period
- 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 are 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)|
|Relative frequency|| || || || |
|Severity|| || || || |
|Age of onset|| || || || |
|Typical features|| |
|Motor milestones|| || || |
|Prognosis|| || || |
The older the age of onset, the better the prognosis!
Type I → non-sitters, type II → sitters, type III → walkers
Definitive therapy 
- Onasemnogene abeparvovec
- Supportive therapy
- 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
- Progressive muscular atrophy: a nonhereditary, adult-onset, progressive lower motor neuron disorder
The differential diagnoses listed here are not exhaustive.