Spinal Muscular Atrophy (SMA)


Spinal muscular atrophy (SMA) is one of the most common genetic conditions affecting children and the No. 1 genetic cause of infant mortality.1 Spinal muscular atrophy life expectancy is highly dependent on the SMA type.

Spinal Muscular Atrophy Life Expectancy by Type

The 5 types of SMA are classified according to the time of symptom onset. Mortality is inversely correlated with age at the onset of SMA.

SMA type 0 is the most severe type, in which symptoms appear even before birth. Infants with SMA type 0 rarely live for more than 6 months. 

In SMA type 1, symptoms usually appear before 6 months of age and include generalized muscle weakness, a weak cry, and difficulty breathing, swallowing, and sucking. Those with SMA type 1, the most common form of the disease, can live up to the age of 2 years but usually die of respiratory failure. 

In SMA type 2, symptoms appear between the ages of 6 and 12 months and consist predominantly of muscle weakness affecting mainly the lower extremities. Patients with SMA type 2 also experience respiratory problems but can live to adulthood with adequate treatment.

The symptoms of SMA type 3 can appear at any time from 18 months of age to early adulthood. In SMA type 3, life expectancy is close to normal.

The symptoms of SMA type 4 do not appear until after the third decade of life, and life expectancy is not different from that of someone without the disease.2

SMA types 0 through 4 are caused by mutations in the SMN1 gene, located on chromosome 5q. 

This gene codes for the survival motor neuron (SMN) protein, which is essential for the health of motor neurons. When cells cannot produce enough SMN protein because of the mutations, motor neurons die and are not able to send electrical signals to the muscles, which also die with time.

Factors Affecting Life Expectancy in SMA

SMA types 0 through 4 are caused by mutations in the SMN1 gene, located on chromosome 5q. This gene codes for the survival motor neuron (SMN) protein, which is essential for the health of motor neurons. When cells cannot produce enough SMN protein because of the mutations, motor neurons die and are not able to send electrical signals to the muscles, which also die with time.

A second, homologous gene, SMN2, also codes for SMN protein. However, because of alternative splicing, most of the protein synthesized from this gene is shorter than normal and nonfunctional. Only approximately 10% to 15% of the SMN protein encoded by the SMN2 gene is functional.3 The copy number of the SMN2 gene varies from person to person and is inversely correlated with the severity of SMA.4 

The SMN2 gene copy number and other genetic modifiers are thought to also influence the life expectancy of SMA patients.5

Disease management can prolong life expectancy in SMA. There are 2 complications that can reduce life expectancy: respiratory problems and feeding issues. 

Because the disease affects respiratory muscles, patients may not be able to breathe without assistance, especially as the disease progresses. They are also more prone to the development of severe respiratory infections. Patients should be monitored for respiratory distress and the level of oxygen saturation in their blood. Some patients may need noninvasive or invasive ventilation.6

Feeding issues can be caused by weakness in the muscles of the mouth and throat. In more severe cases, patients may need a feeding tube to deliver food directly to the stomach or intestine.7 

New disease-modifying treatments [link to Spinal Muscular Atrophy Treatments page] such as nusinersen (Spinraza®) and risdiplam (EvrysdiTM), which aim to increase the production of functional SMN protein encoded by the SMN2 gene, and onasemnogene abeparvovec (Zolgensma®), which delivers a healthy copy of the SMN1 gene to the body, may improve patients’ life expectancy.

Life Expectancy in Non-5q SMA

A small percentage of cases of SMA (4% to 5%) are caused by mutations in genes other than SMN1. These so-called non-5q SMA cases are clinically heterogeneous.8 

For example, SMA with respiratory distress (SMARD) is a severe form of SMA caused by mutations in the IGHMBP2 gene. Symptoms begin between the ages of 6 weeks and 6 months and consist predominantly of  difficulty breathing. Life expectancy without ventilation is up to 13 months.9

Patients with X-linked SMA caused by mutations in the UBA1 gene rarely survive past early childhood, although some affected individuals can survive into adolescence. The main cause of death in these patients is respiratory failure due to chest muscle weakness.10

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

References

  1. Spinal muscular atrophy (SMA). Boston Children’s Hospital. Accessed June 3, 2021.
  2. Types of SMA. Muscular Dystrophy Association. Accessed June 3, 2021.
  3. SMN2 gene. MedlinePlus. Accessed June 2, 2021.
  4. 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:0.3389/fmolb.2016.00007
  5. Lamar KM, McNally EM. Genetic modifiers for neuromuscular diseases. J Neuromuscul Dis. 2014;1(1):3-13. doi:10.3233/JND-140023
  6. Schroth MK. Special considerations in the respiratory management of spinal muscular atrophy. Pediatrics. 2009;123(Suppl 4):S245-9. doi:10.1542/peds.2008-2952K
  7. Chen YS, Shih HH, Chen TH, et al. Prevalence and risk factors for feeding and swallowing difficulties in spinal muscular atrophy types II and III. J Pediatr. 2012;160(3):447-51.e1. doi:10.1016/j.jpeds.2011.08.016
  8. Darras BT. Non-5q spinal muscular atrophies: the alphanumeric soup thickens. Neurology. 2011;26;77(4):312-14. doi:10.1212/WNL.0b013e3182267bd8
  9. Lingappa L, Shah N, Motepalli AS, et al. Spinal muscular atrophy with respiratory distress syndrome (SMARD1): case report and review of literature. Ann Indian Acad Neurol. 2016;19(3):395-8. doi:10.4103/0972-2327.168635
  10. X-linked infantile spinal muscular atrophy. MedlinePlus. Accessed June 2, 2021.
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