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Spinal Muscular AtrophyInformation for Families

This information sheet briefly explains what Spinal Muscular Atrophy (SMA) is and what can cause it. It is written for families where a child, young person or adult has been diagnosed with SMA. It may also be useful for healthcare and other professionals.

SMA is a complex condition; there is a lot of information to take in and every person with SMA is different. Your medical team will always be happy to go over any of this with you.

What is Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is a rare, genetically inherited neuromuscular condition. SMA may affect crawling and walking ability, arm, hand, head and neck movement, breathing and swallowing. SMA is often grouped into ‘Types’. Types of SMA are based on the age at which symptoms first appear and what physical ‘milestones’ a baby or child is likely to achieve. Milestones can include the ability to sit, stand or walk.

There are four main types of SMA: Types 1, 2, and 3 appear in childhood; Type 4 appears in adulthood and is an adult onset form of SMA.

SMA Type 1: This is the most severe form with symptoms usually appearing before a baby is six months old and sometimes before birth. Babies are unable to sit without support. Sadly, usually due to breathing difficulties, without intervention most children with SMA Type 1 rarely survive beyond two years of age.

SMA Type 2: The symptoms of SMA Type 2 usually appear between the ages of 7 and 18 months. Children with SMA Type 2 are unable to stand without support. Though this is a serious inherited neuromuscular condition that may shorten life expectancy, improvements in care standards mean that the majority of people can live long, fulfilling and productive lives.

SMA Type 3: The symptoms of SMA Type 3 appear after 18 months of age. Children are able to stand and walk, although they may need more support with this over time. Life expectancy for children diagnosed with SMA Type 3 is normal1 and most people can live long and productive lives.

SMA Type 4: The symptoms of SMA Type 4 appear in adulthood and may include mild to moderate muscle weakness in the hands and feet and some difficulty with walking. SMA Type 4 is an adult onset form of SMA and is not life-threatening2.

These ‘Types’ are not rigid categories. There is a wide spectrum of severity both between the different types of SMA and between children, young people and adults within each type.

There are also other, even rarer forms of SMA with different genetic causes including SMA with Respiratory Distress (SMARD), Spinal and Bulbar Muscular Atrophy (SBMA) and Distal SMA (DSMA).

For more information on the different types of SMA please see our information sheets.

What causes SMA?

Usually, electrical signals from our brain are sent down our spinal cord along our nerve cells and through to our muscles. This makes it possible for us to consciously contract our muscles and to make them move.

SMA affects a particular set of nerve cells called the lower motor neurons2 which run from the spinal cord out to our muscles. The lower motor neurons carry messages that make it possible for us to move the muscles we use to crawl and walk, to move our arms, hands, head and neck, and to breathe and swallow.

For our lower motor neurons to be healthy we need to produce an important protein called the Survival Motor Neuron (SMN) protein. Our ability to do this is controlled by a gene called Survival Motor Neuron 1 (SMN1)3.

We all have two copies of this SMN1 gene, one from each parent.

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

SMA is passed from parents to their children through their SMN1 genes. When two people who are carriers have a child together their child may inherit two faulty SMN1 genes, one from each parent. If this happens then their child will have SMA.

Having two faulty SMN1 genes means that a child is only able to produce very low amounts of the SMN protein. This causes their lower motor neurons in their spinal cord to deteriorate. Messages from their spinal cord do not efficiently get through to their muscles which makes movement difficult. Their muscles waste due to lack of use and this is known as muscular atrophy.

In addition to SMN1, we possess a second gene that is able to produce some functional SMN protein. This gene is almost identical to SMN1 and is called the SMN2 gene2. However, SMN2 only makes a small fraction of functional protein (about 10%).

For more information on the inheritance of SMA and how SMN2 is linked to the severity of an individual’s SMA please see ‘The Genetics of Spinal Muscular Atrophy’.

There are also other rarer forms of SMA and rarer causes of SMA. Your medical team will be able to provide you with information that applies to your individual situation. You might also want to read SMA Support UK’s leaflet ‘The Genetics of Some Rarer Forms of Spinal Muscular Atrophy’.

In summary:

Figure 1 - How muscle atrophy is caused in SMA

What are the chances of inheriting SMA?

Approximately 1 in every 40 to 60 people carry the faulty SMN1 gene. When two people who are carriers have a child together, the chances for each pregnancy are as follows:

  • Child does not have SMA and is not a carrier: 1 in 4 chance (25%)
     
  • Child does not have SMA but is a carrier: 2 in 4 chance (50%)
     
  • Child has SMA: 1 in 4 chance (25%)

For the purpose of this diagram a ‘non-carrier’ means a person who does not carry the faulty gene and does not have SMA.

Figure 2 – The chances of inheriting SMA when two carriers have a child together

For more information on ‘The Genetics of SMA’ please click here.

Please remember, if your child has a rare form of SMA then this diagram might not necessarily apply to you and your family. If this is the case, your child’s medical team will be able to give you information about your particular genetic situation.

How many people in the UK have SMA?

People think that because SMA is a rare disease we should have an accurate record of how many people there are in the UK with the condition, but this isn’t the case. The exact number of people with the condition is not known for a number of reasons, including: sometimes children and adults have an incorrect diagnosis; we don’t have routine testing of newborn babies; there is no way of testing everyone in the population; there is no central system for collating these statistics.

Instead, scientists take small samples of people and use their findings to make estimates about populations as a whole. Although the reported estimates differ from study to study, the numbers tend to agree that approximately 1 in every 6,000-10,000 babies are born worldwide with the condition4-8. At any one time it is thought that there are between 2,000 – 2,500 children and adults in the UK living with SMA.

How many people carry the faulty SMN1 gene?

Through research, scientists have also been able to estimate that the chances of someone being a carrier is about 1 in 40-609-12.

The population of the UK is around 60 million. So, if you take a carrier frequency of 1 in every 40 people this would suggest that there are approximately 1.5 million people in the UK who have a faulty copy of the SMN1 gene. If you take a carrier frequency of 1 in every 60 people this would suggest approximately 1 million people in the UK are carriers.

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 SMA.

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 very encouraging breakthroughs in developing treatments that increase the production of SMN protein by addressing the genetic fault.

  • Nusinersen

One of these treatments is nusinersen (brand name Spinraza) which essentially targets the SMN2 gene to produce more SMN protein. Nusinersen was developed by pharmaceutical companies Ionis and Biogen which have run clinical trials with infants and children affected by SMA Types 1, 2 or 3.

  • Expanded Access Programme for eligible infants with SMA Type 1

These clinical trials produced interim results that were sufficiently positive for Biogen, in autumn 2016, to open a global ‘compassionate use’ or ‘Expanded Access Programme’ (EAP) for eligible infants with SMA Type 1 who had not been on the trial. Unfortunately, progress with delivering this programme in the UK has been slow, creating immense frustration and distress for families, clinicians and supporting charities.

Any family wanting to explore the possibility of treatment for their child with SMA Type 1 should talk to their medical team about how to do this.

SMA Support UK is working with Muscular Dystrophy UK, the SMA Trust and TreatSMA to progress access to the EAP.  More information on this programme and any updates on what progress there has been is available here.

  • Longer Term Availability 

On June 1st 2017, nusinersen was approved by the European Commission for marketing as a treatment for those with 5qSMA. This is when there is a genetic confirmation of a fault on the SMN1 gene that is found on Chromosome 5. 5qSMA includes SMA Types 1, 2 and 3. It also includes SMA Type 4, a type of Adult Onset SMA. However, there have not yet been any clinical trials of nusinersen with anyone with SMA Type 4.

Nusinersen’s future availability in the UK depends on the National Institute for Health and Care Excellence (NICE), NHS England, the Scottish Medicines Consortium and other authorities in the devolved nations recommending that the NHS funds the drug in England, Scotland, Wales and Northern Ireland. At this stage, it is not known what SMA Types will be considered for possible funding. Availability may also finally depend on the treatment readiness of specialist centres. 

SMA Support UK is working with Muscular Dystrophy UK, the SMA Trust and TreatSMA to progress longer term UK access to all those affected by 5qSMA. To find out more about nusinersen and any updates on what progress there has been towards this, please go to: http://smasupportuk.org.uk/nusinersen

  • Other developments in research

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

 

Version 1.5
Author: SMA Support UK Information Production Team
Reviewed: June 2017
Full review due: September 2017


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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.

References

  1. Montes, J., Gordon, A.M., Pandya, S., De Vivo, D.C. and Kaufmann, P. (2009) ‘Clinical outcome measures in spinal muscular atrophy’, Journal of Child Neurology, 24(8), pp. 968-978.
     
  2. Lunn, M.R. and Wang, C.H. (2008) ‘Spinal muscular atrophy’, The Lancet, 371(9630), pp. 2120-2133.
     
  3. 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. and Melki, J. (1995) ‘Identification and characterization of a spinal muscular atrophy-determining gene’, Cell, 80(1), pp. 155-165.
     
  4. Czeizel, A. and Hamula, J. (1989) ‘A Hungarian study on Werdnig-Hoffmann disease’, Journal of Medical Genetics, 26(12), pp. 761-763.
     
  5. Spiegler, A.W., Hausmanowa-Pertrusewicz, I., Borkowska, J. and KÅ‚opocka, A. (1990) ‘Population data on acute infantile and chronic childhood spinal muscular atrophy in Warsaw’, Human Genetics, 85(2), pp. 211-214.
     
  6. Burd, L., Short, S.K., Martsolf, J.T. and Nelson, R.A. (1991) ‘Prevalence of type I spinal muscular atrophy in North Dakota’, American Journal of Medical Genetics, 41(2), pp. 212-215.
     
  7. Ogino, S., Leonard, D.G., Rennert, H., Ewens, W.J. and Wilson, R.B. (2002) ‘Genetic risk assessment in carrier testing for spinal muscular atrophy’, American Journal of Medical Genetics, 110(4), pp. 301-307.
     
  8. Prior, T.W., Snyder, P.J., Rink, B.D., Pearl, D.K., Pyatt, R.E., Mihal, D.C., Conlan, T., Schmalz, B., Montgomery, L., Ziegler, K., Noonan, C., Hashimoto, S. and Garner, S. (2010) ‘Newborn and carrier screening for spinal muscular atrophy’, American Journal of Medical Genetics, 152A(7), pp. 1608-1616.
     
  9. Cusin, V., Clermont, O., Gérard, B., Chantereau, D. and Elion, J. (2003) ‘Prevalence of SMN1 deletion and duplication in carrier and normal populations: implication for genetic counselling’, Journal of Medical Genetics, 40(4), e39.
     
  10. Sheng-Yuan, Z., Xiong, F., Chen, Y.J., Yan, T.Z., Zeng, J., Li, L., Zhang, Y.N., Chen, W.Q., Bao, X.H., Zhang, C. and Xu, X.M. (2010) ‘Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.’ European Journal of Human Genetics, 18(9), pp. 978-984.
     
  11. Mostacciuolo, M.L., Danieli, G.A., Trevisan, C., Müller, E. and Angelini, C. (1992) ‘Epidemiology of spinal muscular atrophies in a sample of the Italian population’, Neuroepidemiology, 11(1), pp. 34-38.
     
  12. Hendrickson, B.C., Donohoe, C., Akmaev, V.R., Sugarman, E.A., Labrousse, P., Boguslavskiy, L., Flynn, K., Rohlfs, E.M., Walker, A., Allitto, B., Sears, C. and Scholl, T. (2009) ‘Differences in SMN1 allele frequencies among ethnic groups within North America’. Journal of Medical Genetics, 46(9), pp. 641-644.
     
  13. Commission of the European Communities (2008) Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee to the Regions on Rare Diseases: Europe’s challenges. Available at: http://ec.europa.eu/health/ph_threats/non_com/docs/rare_com_en.pdf