Spinal muscular atrophy

Last revised by Dr Yair Glick on 11 Aug 2021

Spinal muscular atrophy is a type of congenital neuromuscular disease affecting anterior horn cells of the brainstem and spinal cord.

This disorder affects 1 in 6000-10000 infants 1.

Spinal muscular atrophy typically affects infants and young children, presenting with progressive, symmetrical, proximal-predominant muscle atrophy and weakness of varying severity 1,2. Although the lower extremities can have greater involvement, axial, intercostal, and bulbar musculature are also frequently involved 1,2.

In infants, the most common demographic affected, this classically manifests as difficulties sitting and rolling, assuming a frog-leg position, a weak cry, and increased respiratory effort with paradoxical breathing 1,3. Rarely is intellectual disability a feature 3

Spinal muscular atrophy is classified into four types with decreasing clinical severity and increasing age of onset 1,2:

  • type 1 (Werdnig-Hoffman disease): infantile form, most severe and most common form, onset before six months
  • type 2: intermediate form, onset between six and twelve months
  • type 3 (Kugelberg-Welander disease): juvenile form, onset after twelve months
  • type 4: adult form

Some authors suggest an additional type 0, also termed 'severe infantile' form, with a prognosis (without novel therapy) of just a few weeks, although this has not been widely adopted in the literature 4

Spinal muscular atrophy has an autosomal recessive mode of inheritance due to mutations to the SMN1 (survival motor neuron 1) gene on chromosome 5 1,2. This mutated gene has a carrier frequency of 1 in 40 1,2.

In muscles, the predominant features are those of muscle atrophy 5,6. Mild types tend to demonstrate fatty infiltration of muscular bundles with increased prominence of intramuscular fat planes 5,6. Intermediate forms may show ragged atrophy of muscles, while the severe forms often show gross atrophy 5,6

In the spinal cord, MRI may reveal T2 hyperintensities in the anterior horns of the cervical cord, and to a lesser degree in the thoracolumbar cord, that are thought to correspond histopathologically to motor neuron loss in these regions 3. These features may resemble the owl's eye sign 3.

Although management was once considered to be mainly supportive, recent advances (as of June 2017) have led to the development of oligonucleotide drugs (e.g. nusinersen) and novel gene therapies (e.g. AVXS-101) which hold promise in improving the quality of life and prognosis of these patients 7-9

Spinal muscular atrophy was originally described in two infant brothers by Austrian neurologist Guido Werdnig (1844-1919) in 1891, and in seven additional cases by German neurologist Johan Hoffmann (1857-1919) from 1893 to 1900 2

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Cases and figures

  • Case 1: type 2, age 10 yrs
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  • Case 2
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