In SMA, there is a loss of important cells in the spinal cord called motor neurons. Motor neurons are essential for control of muscle movement and strength. Motor neurons control 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.
As muscles stop receiving signals from the CNS, symptoms such as progressive muscle weakness and the gradual decrease in the mass and strength of muscles (called atrophy) can develop.
The degeneration of motor neurons leads to the gradual decrease
in the mass and strength of muscles (atrophy).
For illustrative purposes only.
Watch the explanation
A children's story book to help explain SMA and raise awareness of the disease, available for you to download and keep.
Unlike many other rare neuromuscular diseases, there is a clear understanding of the specific genetic cause of SMA.
SMA is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The SMN1 gene is responsible for producing the survival motor neuron (SMN) protein, which plays an important role in maintaining the health and normal function of motor neurons. In individuals with SMA, both copies of the SMN1 gene are mutated, leading to decreased production of SMN protein. Without a sufficient level of SMN protein, motor neurons in the spinal cord will be lost, preventing the muscles from receiving proper signals from the brain.
What are the effects of SMA?
SMA affects everyone differently, and it is important to note that symptoms can vary greatly according to the age of onset and disease severity.
Individuals may experience progressive muscle weakness in the muscles closest to the centre of the body, such as the shoulders, thighs, and pelvis. These muscles are responsible for actions such as:
- head control/movement
- sitting up
Sometimes, breathing and swallowing may also be affected.
It is believed that SMA does not affect the neurons responsible for cognition (the activities of thinking, understanding, learning and remembering). A study has found that children and adolescents with SMA have normal intelligence, with IQs in the standard range.
Find out more about the signs & symptoms of SMA here
What should I know about the SMN2 gene?
All individuals with SMA have at least one “backup gene,” known as SMN2. The SMN2 gene has a similar structure to SMN1 and also produces SMN protein, but only a small amount (10%) of the SMN protein it produces is fully functional. This low level of SMN protein is not enough to sustain the survival of motor neurons in the CNS.
The number of SMN2 genes may vary in individuals, and a higher SMN2 copy number is associated with less-severe symptoms of SMA. However, it is difficult to predict the severity of symptoms based on the number of SMN2 copies alone, therefore experts recommend that care decisions be made on the individual’s functional ability and not on the SMN2 copy number alone.
The discovery of the SMN2 backup gene provides a unique opportunity for researchers, as methods that may help the SMN2 gene produce more SMN protein may lead to potential therapies for SMA.
How is SMA inherited?
SMA is an autosomal recessive disease, which means that for an individual to inherit the disease, 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 SMA.
If you have a family history of SMA, 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, and what appropriate tests may be required to detect these. Once your family mutation(s) are known, an appropriate test for your situation may be determined.
Please speak to your doctor regarding the laboratories and hospitals that may offer SMA carrier screening. Screening can determine whether one or both parents are carriers of the mutated SMN1 gene, and can provide individuals and families with information about the risk of giving birth to a child with SMA. A genetic counsellor is trained to make information about genetic risks, testing, and diagnosis easier for families to understand.
How is SMA managed?
Every individual with SMA will experience symptoms differently, and there are many aspects to care. Experts suggest that a multidisciplinary care approach that includes a variety of medical specialists may help improve overall health and survival. Be sure to ask your healthcare professional if you have any questions about appropriate care options.
For further information about SMA, speak to your healthcare professional.
1. D’Amico A, et al. Orphanet Journal of Rare Diseases. 2011;6:71–81. 2. Butchbach M. Front Mol Biosci. 2016;3:7.
3. Kaczmarek A, et al. Expert Opin Investig. Drugs. 2015;24:867–81.