In spinal muscular atrophy, there is a loss of important cells in the spinal cord called motor neurons, which are essential for muscle strength and movement. These motor neurons regulate muscle activity by sending signals from the central nervous system (CNS), which is the part of the body’s nervous system that includes the brain and spinal cord.1,2
The loss of functioning motor neurons leads to progressive muscle weakness and atrophy (the gradual decrease in the mass and strength of muscles), as muscles stop receiving signals from the CNS.3
Unlike many other rare neuromuscular diseases, there is a clear understanding of the specific genetic cause of spinal muscular atrophy.
What causes spinal muscular atrophy?
Spinal muscular atrophy is caused by a mutation in the survival motor neuron 1 (SMN1) gene. This gene is responsible for producing survival motor neuron (SMN) protein, which maintains the health and normal function of motor neurons. In people with spinal muscular atrophy, both copies of the SMN1 gene are mutated, leading to decreased production of SMN protein. Without a proper level of SMN protein, motor neurons in the spinal cord will be lost, preventing the muscles from receiving proper signals from the brain.5
The degeneration of motor neurons leads to the gradual decrease
in the mass and strength of muscles (atrophy).
For illustrative purposes only.
What does spinal muscular atrophy mean for a child?
Every child with spinal muscular atrophy is affected differently, and it is important to note that symptoms can vary greatly according to the age of onset and disease severity. Children may experience progressive muscle weakness in the muscles closest to the centre of the body, such as the shoulders, thighs, and pelvis. These muscles enable activities such as crawling, walking, sitting up, and controlling head movement. Breathing and swallowing may also be affected.7
SMA is a rare, genetic neuromuscular disease2,5, and SMA is the leading genetic cause of infant and toddler mortality1.
Spinal muscular atrophy does not affect the neurons responsible for cognition, which is the mental process through which we gain knowledge and understanding through thought, experience, and the senses.8.9 According to one study, children and adolescents with spinal muscular atrophy have normal intelligence, with IQs in the standard range.10
What should I know about SMN2?
All individuals with spinal muscular atrophy have at least one “backup gene”, known as SMN2. The SMN2 gene has a similar structure to SMN1, but only a small amount (10%) of the SMN protein it produces is fully functional. This low level of SMN protein is not effective enough to sustain the survival of motor neurons in the CNS.11-13
The number of SMN2 genes may vary, and a higher SMN2 copy number is associated with less-severe symptoms of spinal muscular atrophy.5,13,14 The disease has a wide range of symptoms and, although there is a strong correlation between SMN2 copies and disease severity, there are exceptions. Experts therefore recommend that care decisions are made based on the child's functional ability, and not on SMN2 copy number. However, SMN2 copy number is used as a key criteria for enrolment in clinical trials.2,15
How is spinal muscular atrophy inherited?
Spinal muscular atrophy is an autosomal recessive disease, which means that for a child to be at risk, he or she must inherit 1 mutated SMN1 gene from each parent. If a child inherits only 1 mutated SMN1 gene, they are considered a “carrier”, but usually do not have symptoms of spinal muscular atrophy.16
If you have a family history of spinal muscular atrophy, your chances of being a carrier are greater than average. In making reproductive decisions, it may be helpful to consult with your physician to learn what mutation(s) are common in your family. Once your family mutation(s) are known, an appropriate test for your situation may be determined:
- If your family mutation(s) are SMN1 deletions, then copy number testing may be appropriate for you
- If your family mutation(s) include a more subtle change in the gene, then your physician and the laboratory may decide whether testing can be done to look for that specific change
If you are unable to obtain your family mutation(s) information, you can still have a copy number test performed. Your chance of being a carrier (before you have testing) will be calculated from your family history. If your results are normal, your chance of being a carrier may be lower.
Many laboratories and hospitals offer carrier screening to determine whether 1 or both parents are carriers of the mutated SMN1 gene. This can provide individuals and families with information about the risk of giving birth to a child with spinal muscular atrophy.17 A genetic medical counsellor is trained to make information about genetic risks, testing, and diagnosis easier for families to understand.
Understand the role of a genetic medical counsellor here
1. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371(9630):2120-2133. 2. Wang CH, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049. 3. National Institute of Neurological Disorders and Stroke. Motor Neuron Disease Fact Sheet. 2012. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Motor-Neuron-Diseases-Fact-Sheet. Accessed January 9, 2017. 4. Genetics Home Reference. SMN1 gene. 2012. Available at: https://ghr.nlm.nih.gov/gene/SMN1. Accessed January 9, 2017. 5. Genetics Home Reference. SMN2 gene. 2012. Available at: https://ghr.nlm.nih.gov/gene/SMN2. Accessed January 9, 2017. 6. Biogen Inc. Data on file. 7. Finkel R, et al. 209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy 7-9 November 2014, Heemskerk, The Netherlands. Neuromuscul Disord. 2015;25(7):593-602. 8. Cure SMA. At School. 2016. Available at: http://www.curesma.org/support-care/living-with-SMA/daily-life/at-school/. Accessed January 9, 2017. 9. National Organization for Rare Disorders. Werdnig-Hoffman Disease. 2012. Available at: https://rarediseases.org/rare-diseases/werdnig-hoffmann-disease/. Accessed January 9, 2017. 10. Neuromuscul Disord. 2002 Feb;12(2):130-6. Intelligence and cognitive function in children and adolescents with spinal muscular atrophy. von Gontard at al. 11. Cure SMA. Cure SMA Medical Provider Information Kit. Available at: http://www.curesma.org/documents/support--care-documents/2016-sma-awareness-mpak.pdf. Accessed January 9, 2017. 12. Cherry JJ, et al. Identification of novel compounds that increase SMN protein levels using an improved SMN2 reporter cell assay. J Biomol Screen. 2012;17(4):481-495. 13. Darras BT, Royden Jones H Jr, Ryan MM, De Vivo DC, eds. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. 2nd Ed. London, UK: Elsevier; 2015. 14. Prior TW. Perspectives and diagnostic considerations in spinal muscular atrophy. Genet Med. 2010;12(3):145-152. 15. TREAT-NMD. Diagnostic testing and care of new SMA patients. Available at: http://www.treat-nmd.eu/downloads/file/standardsofcare/sma/english/sma_soc_en.pdf. Accessed January 9, 2017. 16. National Organization for Rare Disorders. Spinal Muscular Atrophy. 2012. Available at: https://rarediseases.org/rare-diseases/#causes. Accessed January 9, 2017. 17. Quest Diagnostics. SMA Carrier Screen. 2013. Available at: http://www.questdiagnostics.com/testcenter/testguide.action%3Fdc%3DTS_SMA. Accessed January 9, 2017.