Tel: 01789 267520

Spinal Muscular Atrophy – Key Information

This information sheet is written for anyone wanting to know more about Spinal Muscular Atrophy (SMA).

What is Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is a rare, genetically inherited neuromuscular condition. It causes progressive muscle weakness and loss of movement due to muscle wasting (atrophy). This may affect crawling and walking ability, arm, hand, head and neck movement, breathing and swallowing. There are different forms of SMA and a wide spectrum of how severely children, young people and adults are affected.

The more common forms of SMA are often described as ‘Types’. Symptoms of SMA Types 1, 2 and 3 begin at different ages in childhood. SMA Type 4 is an adult onset form.  The impact of the condition, however, varies greatly within and between each type. Sometimes to try to describe this, doctors will add ‘a’, ‘b’ or ‘c’1 to the type of SMA or, as well as being diagnosed with ‘type’, a child may also be described as ‘strong’ or weak’ or having ‘early onset’ or ‘later onset’. A child / young person’s ability to sit, stand or walk and how their breathing ability is affected by their SMA are all also very important – especially when it comes to managing the condition. 

Broadly speaking, and bearing all this in mind, each type of SMA is currently understood to be as follows:

  • SMA Type 1: symptoms usually begin between the ages of 0 and 6 months. It’s the most severe form of SMA; generally, the earlier the onset of symptoms, the more severe the condition. Babies are unable to sit without support and may be described as ‘non sitters’. It is not possible to predict life expectancy accurately but, due to breathing difficulties, without intervention this has usually been less than two years.
     
  • SMA Type 2: symptoms usually begin between the ages of 7 and 18 months. Children are unable to stand without support and may be described as ‘sitters’. Their weak respiratory muscles can make it difficult for them to cough effectively, which can make them more vulnerable to chest (respiratory) infections. Though this is a serious neuromuscular condition that may shorten life expectancy2, improvements in care standards mean that the majority can live long, fulfilling lives. 
     
  • SMA Type 3a: symptoms usually begin between 18 months and 3 years of age. Children can stand and walk, although this will become more difficult and they will need more support with this over time. In SMA Type 3b, symptoms usually begin after 3 years. Difficulties with standing and walking usually occur later than for children who have earlier symptoms. Depending upon the individual impact of their condition, children and adults with SMA Type 3 may be described as ‘sitters’ or ‘walkers’. They don’t usually have breathing problems, their life expectancy is not affected3 and most can live long, fulfilling lives.
     
  • SMA Type 4: symptoms begin in adulthood and include mild to moderate muscle weakness in the arms and legs and some difficulty walking. SMA Type 4 is not life-threatening4. It is a form of Adult Onset SMA.

For more information about diagnosis and management of these forms of SMA and other even rarer forms of childhood and Adult Onset SMA, visit: www.smasupportuk.org.uk/about-sma

What causes the main types of SMA?

  • The SMN1 gene

The main types of SMA affect the nerve cells called lower motor neurons which reside in the spinal cord and project out to the muscles. These lower motor neurons carry electrical signals from the brain to move the muscles used for crawling and walking. These signals also control movement of arms, hands, head and neck as well as breathing and swallowing. For these lower motor neurons to be healthy, our Survival Motor Neuron 1 genes (SMN1 genes5) must produce enough Survival Motor Neuron (SMN) protein.

Most people have two copies of the SMN1 gene. People with the main types of SMA have two faulty copies of the SMN1 gene, which means they are unable to produce enough SMN protein to have healthy lower motor neurons4. This causes their lower motor neurons in the spinal cord to deteriorate. This restricts the delivery of signals from the brain to their muscles, making movement difficult. Their muscles then waste due to lack of use; this is known as muscular atrophy.

In summary:

The SMN1 gene is on the fifth chromosome in the region labelled ‘q’. This is why the main types of SMA are often referred to as ‘5q SMA’.

  • The SMN2 gene5

A second gene also has a role in producing SMN protein. This is the Survival Motor Neuron 2 gene (SMN2), sometimes referred to as the SMA “back-up gene”. 

However, most of the SMN protein produced by SMN2 lacks a key building block that is usually produced by SMN1. This means that SMN2 cannot fully make up for the faulty SMN1 gene in people with SMA. 

The number of SMN2 genes can vary greatly from person to person, from 0 – 8 copies6-8. The severity of SMA has been linked to how much SMN protein a person makes6-8; individuals with more SMN2 copies typically have a less severe form of SMA than those with fewer copies.

How do people get SMA?

SMA is an autosomal, recessive, inherited neuromuscular condition. It is passed from parents to their children through faulty SMN1 genes:

  • People who have inherited two faulty copies of the SMN1 gene (one from each parent) have SMA.
     
  • People who have inherited one faulty copy and one healthy copy of the SMN1 gene (one from each parent) are carriers of SMA. Carriers usually do not have SMA or any symptoms of SMA.
     
  • People who have inherited two healthy copies of the SMN1 gene (one from each parent) do not have SMA and are not carriers.

When two SMA carriers have a child together, for each pregnancy there is a:

  • 1 in 4 (25%) chance that the child will inherit both faulty copies of the SMN1 gene and will develop SMA.
     
  • 1 in 2 (50%) chance that the child will inherit one faulty copy and one healthy copy of the SMN1 gene and will be a carrier.
     
  • 1 in 4 (25%) chance that the child will inherit two healthy copies of the SMN1 gene and will not be a carrier or have SMA.

In around 2% of cases of SMA, the mutation is new in the affected person, most likely due to an error in making the egg or sperm cell from which they were conceived.  This is called a de novo mutation

For more detailed information, please see our information sheet: The Genetics of SMA.         

How many people are affected?

Approximately 1 in 40 people carry the faulty SMN1 gene9 -  that means there are around 1.6 million carriers in the UK.

The incidence is the number of new cases of a condition or disease at any one time. Recent studies indicate that approximately one in every 10,000 babies worldwide are born with a type of SMA and that Type 1 SMA accounts for approximately 60% of cases9,10.

In the UK in 2016, there were 774,835 live births11-13. This suggests that in that year approximately 78 babies were born with a type of SMA.

The prevalence is how many people are living with a condition or disease in a population at any one time. Recent studies suggest between 1 and 2 people in every 100,000 worldwide have a type of SMA9,10.

In 2016, the UK population was 65.6 million14. Based on this, it is estimated that between 650 and 1300 people have SMA in the UK at any one time. Previous estimates by clinicians have suggested an upper limit likely to be 2,500. As there is no central information source, the exact numbers are unknown.

Is there a treatment or cure?

Although there is currently no cure for SMA, this does not mean that nothing can be done. There are a range of options aimed at managing symptoms, reducing complications of muscle weakness and maintaining the best quality of life. These are outlined in the internationally agreed Standards of Care for SMA8,15

  • Nusinersen / SpinrazaTM

The first (and currently, the only) potentially available drug treatment for SMA is called nusinersen. Essentially, the drug is designed to modify the product of the SMN2 gene to produce more functional SMN protein.

In collaboration with researchers, nusinersen was developed by Ionis Pharmaceuticals and Biogen Idec, which have run clinical trials with infants and children affected by SMA Types 1, 2 or 3. There have not yet been any clinical trials of nusinersen with anyone with SMA Type 4. On June 1st, 2017, the European Commission approved nusinersen for marketing under its brand name SpinrazaTM as a treatment for those with 5q SMA16. This is a broad term, that includes SMA Types 1, 2, 3 and 4. 

Currently in the UK, nusinersen is only available if the medical team and family agree that an infant with SMA Type 1 is eligible and may potentially benefit from the treatment. This is possible in Scotland via the NHS and in the rest of the UK via what is called an Expanded Access Programme (EAP).

To find out more about how nusinersen works and the clinical trial results, please explore this section of our website. Here, you will also find out how the UK drug approval system works, what stage nusinersen has reached, and the collaborative efforts being made to widen access to the treatment.

  • Research and further developments

There is a considerable amount of research into SMA taking place around the world. This research will not only improve our understanding of the condition, but will also help to develop effective treatments.

One area of extensive research is the genetics of SMA and the underlying mechanisms that lead to damage of the nerve cells. The UK is a significant contributor to this, with several UK centres involved in clinical trials and international collaborations. This has led to encouraging breakthroughs in developing treatments.

SMA Support UK’s website also notifies the SMA community about the latest developments with other drug treatments, the science behind them, and what clinical trials and other research is going on here . We alert people to new postings via our social media and monthly E-news. You can sign up for mailings here.     

Further Resources

SMA Support UK information:

You will find a wide range of leaflets and resources in this section of the website:

Standards of Care for Spinal Muscular Atrophy (2017)

You can read about and download the 2017 internationally agreed Standards of Care  here

References

  1. Finkel, R.S., Sejersen, T.,Mercuri, E., on behalf of the ENMC SMA Workshop Study Group, 218th ENMC International Workshop: Revisiting the Consensus on Standards of Care in SMA February 19 – 21, 2016, Naarden, The Netherlands, NeuromuscularDisorders (2017), http://dx.doi.org/doi: 10.1016/j.nmd.2017.02.014
     
  2. Farrar MA, Vucic S, Johnston HM, duSart D, Kiernan MC (2013) Pathophysiological insights derived by natural history and motor function of spinal muscular atrophy. J Pediatrics 162: 155-159.
     
  3. Zerres K, Rudnik-Schöneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I (1997) A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci 146: 67-72.
     
  4. Lunn MR, Wang CH (2008) ‘Spinal muscular atrophy’, Lancet, 371: 2120-2133.
     
  5. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, Le Paslier D, Frézal J, Cohen D, Weissenbach J, Munnich A, Melki J (1995) Identification and characterization of a spinal muscular atrophy-determining geneCell 80: 155-165.
     
  6. Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J (1997). Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16: 265–269.
     
  7. Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AHM, Prior TW (2002). Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med 4: 20–26.
     
  8. Eugenio Mercuri, et al., Diagnosis and management of spinal muscular atrophy: Part 1 Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disorders (2017), doi: 10.1016/j.nmd.2017.11.005 www.sciencedirect.com/science/article/pii/S0960896617312841?via%3Dihub
     
  9. Verhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC, Cook SF, Lochmüller H (2017) Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy –a literature review. Orphanet J Rare Dis 12: 124.
     
  10. Verhaart IEC, Robertson A, Leary R, McMacken G, König K, Kirschner J, Jones CC, Cook SF, Lochmüller H. (2017) A multi-source approach to determine SMA incidence and research ready population. J Neruol 264: 1465-1473.
     
  11. Office of National Statistics (2017) ‘Births in England and Wales: 2016’. Available at:
    https://www.ons.gov.uk/peoplepopulationandcommunity/births
    deathsandmarriages/livebirths/bulletins/birthsummarytablesenglandand
    wales/2016
    (Accessed:11 March 2018)
     
  12. National Records of Scotland (2017) ‘Births, Death and other Vital Events: Preliminary figures for 2016’. Available at: https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/general-publications/births-deaths-and-other-vital-events-preliminary-annual-figures/2016 (Accessed: 11 March  2018)
     
  13. Northern Ireland Statistics and Research Agency (2017) 'Monthyl births’. Available at: www.nisra.gov.uk/publications/monthly-births(Accessed:11 March 2018)
     
  14. Office for National Statistics ‘Overview of the UK Population: July 2017.’ Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/
    populationandmigration/populationestimates/articles/overview
    oftheukpopulation/july2017#main-points
    (accessed 11 March 2018)
     
  15. Richard S. Finkel, et al., Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organs systems; and ethics, Neuromuscular Disorders (2017), doi: 10.1016/j.nmd.2017.11.004 www.sciencedirect.com/science/article/pii/S0960896617312907?via%3Dihub  
  16. Wang CH, Finkel RS, Bertini ES, Schroth M, Simonds A, Wong B, Aloysius A, Morrison L, Main M, Crawford TO, Trela A; Participants of the International Conference on SMA Standard of Care (2007) Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 22: 1027-1049. Available at: www.treat-nmd.eu/care/sma/care-standards/ (Accessed: 11 March 2018)
  17. European Medicines Agency (2017) ‘Committee for Medicinal Products for Human Use Assessment Report Spinraza’ (EMA/289068/2017). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004312/WC500229706.pdf
    (Accessed: 11 March 2018)
     

Version 3.5
Author: SMA Support UK Information Production Team
First published: September 2017

Updated: May 2018
Next full review due: September 2020

 

Please help us keep on producing information like this.

Donate

If you have any feedback about this information, please do let us know at supportservices@smasupportuk.org.uk

You can sign up as an information publication reviewer by contacting us by email: supportservices@smasupportuk.org.uk or phoning: 01789 267 520.

We are grateful to the writers and reviewers who assist us in our information production. A list of who this includes may be viewed here

Whilst every effort is made to ensure that the information in this document is complete, correct and up to date, this cannot be guaranteed and SMA Support UK shall not be liable whatsoever for any damages incurred as a result of its use. SMA Support UK does not necessarily endorse the services provided by the organisations listed in our information sheets.