Spinal Muscular Atrophy (SMA)


Spinal Muscular Atrophy Prognosis by Disease Type

Spinal muscular atrophy (SMA) can severely affect a patient’s life expectancy. The prognosis depends on the SMA type that has been diagnosed. For example, life expectancy for 95% of patients with the most common type of SMA, type 1, is less than 18 months.1 The life expectancy of those with the adult-onset form of the disease, SMA type 4, is no different from that of persons without the disease.2

SMA Type 0 Prognosis

Babies in whom SMA type 0, the most severe type, is diagnosed at birth usually do not live past the age of 6 months and may live no longer than 1 month.3 The cause of death is usually respiratory failure, even with respiratory support. Congenital heart defects may also play a role.

SMA Type 1 Prognosis

When symptoms appear within 6 months after birth, SMA type 1 is diagnosed. This accounts for approximately 50% to 70% of all cases of SMA.1 Life expectancy is usually less than 2 years for patients with SMA type 1. Respiratory failure is often the main cause of death.

SMA Type 2 Prognosis

Among patients with SMA type 2, symptoms generally appear between the ages of 6 and 12 months. These patients can live into late childhood or adulthood with adequate treatment.4 

SMA Type 3 Prognosis

In patients with a diagnosis of SMA type 3, symptoms can appear at any time from 18 months of age to early adulthood. Although frequent respiratory infections are common owing to respiratory muscle weakness, life expectancy is close to normal.5

SMA Type 4 Prognosis

In SMA type 4, or adult-onset SMA, symptoms usually appear after the third decade of life. The disease does not usually affect respiratory muscles or those involved in swallowing. The life expectancy of patients with SMA type 4 is the same as that of the rest of the population.2 

Factors Affecting SMA Prognosis

Several factors can affect the prognosis of a patient with SMA. These include the patient’s age at the onset of symptoms, the SMN2 gene copy number, genetic modifiers, and the therapeutic support provided.

As a general rule, the earlier the symptoms appear, the worse the SMA prognosis. The more functional abilities the patient achieves, the better the prognosis.

The number of SMN2 gene copies can also affect prognosis, although it is not as reliable a predictor as age at disease onset.6 SMA is caused by homozygous deletion or various mutations in the SMN1 gene.7 This gene is responsible for the production of most of the functional SMN protein in the body. SMN protein is essential for the survival of motor neurons.

Humans also have a second gene, SMN2, which codes for 10% to 15% of their functional SMN protein.8 The rest is shorter than normal as a consequence of alternative splicing and is rapidly destroyed. The copy number of the SMN2 gene varies from one person to another.6 A higher copy number means that more functional SMN protein can be expressed. This can, in turn, increase life expectancy. The SMN2 copy number is also used as an inclusion criterion in SMA clinical trials.6 

Research suggests that other genetic modifiers may affect spinal muscular atrophy prognosis, as the clinical presentations of siblings who are haplo-identical in terms of SMN2 copy number may differ. One such genetic modifier is the plastin 3 gene (PLS3).6 Some studies have shown that levels of PLS3 mRNA are higher in female patients with relatively mild SMA than in their siblings with a more severe clinical presentation. However, another study showed that female siblings with a relatively severe SMA phenotype had higher levels of PLS3 mRNA.9

Finally, the treatment that a patient receives can affect disease spinal muscular atrophy prognosis.10 For those with SMA type 1 or 2, breathing support with a ventilator can facilitate breathing and prolong life expectancy. Breathing support can be noninvasive, such as via a bilevel positive airway pressure device, or invasive, such as through a tracheostomy. The choice between one or the other type of breathing support can be difficult and should be discussed with the family according to their needs and the course of care. Whereas patients with milder disease can usually manage with noninvasive breathing support, those with more severe disease may need greater assistance and invasive ventilation. Careful monitoring to detect respiratory infections and treating them adequately are also important and can improve the prognosis. 

A feeding tube can ensure that the patient receives adequate nutrition and prolongs life expectancy.11 For those with less severe symptoms, physiotherapy and occupational therapy can improve overall health and may prolong life expectancy. For patients with type 3 or type 4 disease, regular exercise is important and, along with a balanced diet, can help them maintain a healthy weight.

Disease-modifying treatments such as nusinersen (Spinraza®), onasemnogene abeparvovec (Zolgensma®), and risdiplam (Evrysdi™) can affect the prognosis of patients with SMA.12 These treatments address the underlying cause of the disease and in several studies have been shown to increase lifespan, especially if treatment is begun early.

Reviewed by Michael Sapko, MD on 7/1/2021

References

  1. Type 1. SMA Europe. Accessed June 4, 2021.
  2. Spinal muscular atrophy type 4. Genetic and Rare Disease Information Center. Accessed June 4, 2021.
  3. Types of SMA. Muscular Dystrophy Association. Accessed June 4, 2021.
  4. Spinal muscular atrophy (SMA). Boston Children’s Hospital. Accessed June 4, 2021.
  5. Montes J, Gordon AM, Pandya S, De Vivo DC, Kaufmann P. Clinical outcome measures in spinal muscular atrophy. J Child Neurol. 2009;24(8):968-78. doi:10.1177/0883073809332702
  6. Butchbach MER. Copy number variations in the survival motor neuron genes: implications for spinal muscular atrophy and other neurodegenerative diseases. Front Mol Biosci. 2016;10;3:7. doi:10.3389/fmolb.2016.00007
  7. Spinal muscular atrophy fact sheet. National Institute of Neurological Disorders and Stroke. Accessed June 4, 2021. 
  8. SMN2 gene. Medline Plus. Accessed June 4, 2021.
  9. Bernal S, Also-Rallo E, Martínez-Hernández R, et al. Plastin 3 expression in discordant spinal muscular atrophy (SMA) siblings. Neuromuscul Disord. 2011;21(6):413-9. doi:10.1016/j.nmd.2011.03.009
  10. Treatment: spinal muscular atrophy. NHS. Accessed June 4, 2021.
  11. Nutrition basics. Cure SMA. Accessed June 4, 2021.

Treating SMA. Cure SMA. Accessed June 4, 2021.

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