What is 5q Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is a rare, genetic neuromuscular condition causing progressive muscle wasting (atrophy) and weakness leading to loss of movement. 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 and adults are affected.

The most common form is known as ‘5q SMA’; the term ‘5q’ refers to its genetic cause. When a child or adult is first diagnosed with 5q SMA, the doctor gives a clinical classification - SMA Type 1, 2, 3 or 4 - which reflects the age of onset of symptoms and the motor milestones that someone would be expected to achieve. Drug treatments are starting to change these expectations.

Information about some of the rarer forms of SMA that have different genetic (non-5q SMA) causes can be found here.

This page tells you more about 5q SMA:

SMA Types 1, 2, 3 & 4

What causes 5q SMA?

How is it inherited?

How many people are affected?

Is there a treatment or cure?

As you read this guide, please remember that:

  • Although 5q SMA is clinically classified into different ‘Types’ which reflect the potential severity of its impact, it is considered a spectrum.
     
  • For children and adults, the severity of the condition varies from person to person, both within and between ‘Types’ - each child and adult is affected differently.
     
  • Care and management as recommended in the ‘International Standards of Care for SMA’1-3 should always be provided.
     
  • The physical milestones describing people’s ability to sit, stand and walk are increasingly important when it comes to making decisions about care and how to manage symptoms.
     
  • For simplicity, the summary words ‘non-sitters’, ‘sitters’ and ‘walkers’ are often used.
     
  • Treatments that may change the impact of a person’s 5q SMA are starting to become available.
     

Current clinical classification of ‘Types’

There is a wide spectrum of how severely children, young people and adults are affected, both within and between ‘Types’. Broadly, though, they are as follows:

*Adapted from Finkel et al., 20174

SMA Type 1 is the most severe form of SMA. Symptoms of muscle weakness usually begin between 0 and 6 months. Infants are unable to sit without support and may be described by clinicians as ‘non-sitters’. They also often have feeding and breathing difficulties due to rheir weak muscles. Generally, the earlier the onset of symptoms, the more severe the condition.

Before 2007, without intervention for breathing difficulties, most children were expected to live for less than two years5. The November 2017 ‘International Standards of Care for SMA’ refer to evidence that suggests that since more proactive managements were introduced in 2007, children have been living longer1,2.

You can read more about the symptoms, diagnosis and effects of SMA Type 1 here. If you are a parent or carer, you may find it helpful to read our guide: ‘Looking after your child who has had a recent diagnosis of SMA Type 1’.

Our Living With SMA website area has a wide range of information and ideas for daily living.

Since late 2016, the gradual worldwide introduction of drug treatments has been further changing outcomes positively for children who have SMA Type 1, especially for newly diagnosed infants. In general, both clinical trial and real-world evidence suggests that early treatment is necessary to maximise the potential benefits.

Global clinical trials and follow-up studies of possible drug treatments for those who have SMA Type 1 had tended to focus on their impact on motor milestones and survival. There is more understanding now of the importance of respiratory outcomes, and the value of other outcomes, that impact on a child’s quality of life, such as the development of: swallowing, feeding / eating; verbal communication; muscle support of spine and hips; fine motor skills and fatigue levels.

In the UK, drug treatment (NHS funded) is now possible for many children who have SMA Type 1. If you are a parent or carer, you may find it helpful to read our guide.

To keep up-to-date with the latest developments in research and drug treatments, please visit this page.


SMA Type 2: symptoms usually begin between 7 and 18 months of age. Children and adults are unable to stand without support and may be described by clincians as ‘sitters’. Their swallowing and breathing muscles may or may not be affected. If someone’s breathing muscles are affected, this can make it difficult to cough effectively, which can make them more vulnerable to chest (respiratory) infections. Though this is a serious complication that is associated with reduced life expectancy6, improvements in healthcare standards mean that the majority of people live long, fulfilling lives.

You can read more about the symptoms, diagnosis and effects of SMA Type 2 here. If you are a parent or carer, you may find it helpful to read our guide: ‘Looking after your child who has had a recent diagnosis of SMA Type 2'.

Our Living With SMA website area for parents, teenagers and adults has a wide range of information and ideas for daily living.

Since late 2016, the gradual worldwide introduction of drug treatment for children and adults who have SMA Type 2 has seen positive outcomes. In general, both clinical trial and real-world evidence suggests that early treatment is necessary to maximise the potential benefits.

Global clinical trials and follow-up studies of possible drug treatments for those who have SMA Type 2 had tended to focus on their impact on motor milestones gained in childhood.There is more understanding now of the importance of respiratory outcomes, and the value of other outcomes, that impact on quality of life for older children, young people and adults, such as fine motor skills and fatigue levels which enable or maintain independence in daily living. In 2019, 96.7% of 1,327 validated responses to SMA Europe’s survey of people diagnosed with SMA stated they would “consider it to be progress if there was a drug to stabilize their current clinical state.”7

In the UK, drug treatment (NHS funded) is now possible for some children and adults who have SMA Type 2.

To keep up-to-date with the latest developments in research and drug treatments, please visit this page.  


SMA Type 3a: symptoms usually begin between 18 months and 3 years of age. Children can stand and walk, although this becomes more difficult with age and they will need more support over time.

In SMA Type 3b, symptoms usually begin after 3 years. Difficulties with standing and walking usually occur later than they do for children with SMA Type 3a.

Depending upon the individual impact of their condition, children and adults with SMA Type 3 may be described as ‘sitters’ or ‘walkers’.

Fewer people with SMA Type 3 have breathing or swallowing symptoms as swallowing and breathing muscles are not usually affected. Life expectancy isn’t usually affected8 and most live long, fulfilling lives.

You can read more about the symptoms, diagnosis and effects of SMA Type 3 here. If you are a parent or carer, you may find it helpful to read our guide: ‘Looking after your child who has had a recent diagnosis of SMA Type 3'.

Our Living With SMA website area for parents, teenagers and adults has a wide range of information and ideas for daily living.

Since late 2016, the gradual worldwide introduction of drug treatment for children and adults who have SMA Type 3 has seen positive outcomes. In general, both clinical trial and real-world evidence suggests that early treatment may be necessary to maximise the potential benefits.

Global clinical trials and follow-up studies of possible drug treatments for those who have SMA Type 3 had tended to focus on their impact on motor milestones gained in childhood.  There is more understanding now of the value and importance of respiratory and other outcomes that impact on quality of life for older children, young people and adults, such as fine motor skills and fatigue levels which enable or maintain independence in daily living. In 2019, 96.7% of 1,327 validated responses to SMA Europe’s survey of people diagnosed with SMA stated they would “consider it to be progress if there was a drug to stabilize their current clinical state.”7

In the UK, drug treatment (NHS funded) is now possible for some children and adults who have SMA Type 3.

To keep up-to-date with the latest developments in research and drug treatments, please visit this page.  


SMA Type 4: symptoms begin in adulthood and include mild to moderate muscle weakness in the arms and legs and some difficulty walking. It rarely affects swallowing and breathing. SMA Type 4 usually progresses slowly over time causing increased muscle weakness with age. This may impact on daily living activities such as walking, dressing and bathing. SMA Type 4 isn’t life-limiting9.

SMA Type 4 affects the lower motor neurons. This is different from Motor Neurone Disease (MND), also known as Amyotrophic Lateral Sclerosis (ALS), which affects both the upper and lower motor neurons. Though SMA is also classed as a motor neuron disease, it isn’t MND. Whereas MND is almost always life-threatening, SMA Type 4 isn’t.

You can read more about the symptoms, diagnosis and effects of SMA Type 4 here. Our guide, ‘Looking after yourself if you are an adult who has had a recent diagnosis of SMA’ answers many questions asked by adults newly diagnosed with SMA Type 4.

Our Living With SMA website area has a wide range of information and ideas for daily living for adults.

Access to treatments for those clinically diagnosed with SMA Type 4 varies between countries. This may depend on the decision made by the regulatory authorities – for example in some countries it is approved for all who have 5q SMA. It may also depend on how distinct the ‘onset of symptoms’ age boundary is considered to be between Type 3b and Type 4.

In the UK now, access to drug treatment (NHS funded) is only possible for those who have a clinical diagnosis of SMA Type 1, 2 or 3 (see table page 1) and who meet other eligibility criteria. No drug treatments are currently available in the UK for people who have been given the clinical classification / diagnosis SMA Type 4, which should include careful review of the history of the person’s onset of symptoms.

Support and advice can help manage the symptoms and effects.
 

What causes 5q SMA?

  • The SMN1 gene10

All Types of 5q SMA affect the nerve cells called lower motor neurons. These are found within the spinal cord and transmit signals to muscles. Lower motor neurons carry electrical signals from the brain to activate the muscles used for movements, such as crawling and walking. These signals control movement of arms, hands, head and neck, as well as breathing and swallowing. For these nerve cells to be healthy, our Survival Motor Neuron 1 (SMN1) genes10 must produce enough Survival Motor Neuron (SMN) protein.

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

Most people have two copies of the SMN1 gene. People with 5q SMA have two faulty copies of the SMN1 gene, which means they are unable to produce enough SMN protein to have healthy lower motor neurons9. This means that these specialist nerve cells in the spinal cord deteriorate, which restricts the delivery of signals from the brain to the muscles, making movement difficult. The muscles then waste due to lack of use - this is known as muscular atrophy.

In summary:

  • The SMN2 gene10

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, while SMN2 can make some functional SMN protein, it cannot fully make up for the faulty SMN1 gene in people who have SMA. 

It’s estimated that only about 10% of the SMN protein 
made from SMN2 is functional. The large majority (about 90%) of protein produced from SMN2 is lacking an essential part and is consequently non-functional13

Unlike most genes, the number of copies of SMN2 on each chromosome can vary from one person to the next11; there can be between 0 – 8 copies. At a population level, the severity of SMA is linked to how much SMN protein is made11,12; there is therefore a general relationship between the number of SMN2 copies (‘SMN2 copy number’) and the likely severity of SMA symptoms11,12. Having more SMN2 copies is generally associated with less severe SMA symptoms. However, at an individual level, accurate predictions cannot be made about the Type or severity of SMA based on the SMN2 copy number alone1,2. This is likely to be because other genetic, and possibly environmental, factors have an influence on the disease. 

Bearing this in mind, the following table gives a summary of:

  • how many SMN2 copies the majority of people within each Type of SMA may have (see ‘usual number’ column), and
     
  • the possible range of copy numbers that people within each Type of SMA may have (see ‘range’ column)
SMA Type Usual age of symptoms3 SMN2 copies
'usual number'2 'range'12
Type 1 Younger than 6 months 2 1-3
Type 2 6-18 months 3 2-4
Type 3a Under 3 years 3 3-5
Type 3b Over 3 years 4  
Type 4 Over 18 years 4-6  
Table adapted from Tillmann et al. 201814
 

How do people inherit 5q SMA?

5q SMA is passed from parents to their children through faulty SMN1 genes. It usually follows an autosomal, recessive pattern of inheritance. This means that:

  • 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 don’t have SMA or any symptoms of SMA.
     
  • People who have inherited two healthy copies of the SMN1 gene (one from each parent) don’t have SMA and aren’t 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 have 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 and means that at least one parent is not a carrier.

 

For more detailed information, please see our information sheet, ‘The Genetics of 5q SMA’.


How many people are affected by SMA?

Approximately 1 in 40 people carry the faulty SMN1 gene15 - that means there are around 1.67 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 SMA Type 1 accounts for approximately 60% of cases15,16.

In the UK in 2020, there were 681,560 live births17-19. This suggests that in that year, approximately 68 babies were born with a Type of 5q 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 SMA15,16 (which equates to between 10 and 20 people in every million).

In 2020, the UK population was approximately 67.1 million20. Based on this, it is estimated that between 670 and 1340 people have SMA in the UK at any one time. As there is no central information source the exact numbers are unknown.

In 2018, Public Health England (PHE) started to collect data about people diagnosed with SMA in England, through the National Congenital Anomaly and Rare Disease Register (NCARDRS). In September 2019, they published their first report containing preliminary prevalence data on Spinal Muscular Atrophy Type 1. This was based on Hospital Episode Statistics (HES), Office of National Statistics (ONS) mortality data and patient data held by the NCARDRS.

In Public Health England’s 2019 report, they estimated that 1 in 16,320 babies born in England have SMA Type 1 (around 42 babies per year)21.


Is there a treatment or cure for 5q SMA?

The International Standards of Care for SMA1-3

Although there is currently no cure for SMA, this doesn’t 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 SMA1-3, which were updated by experts and patient representatives and published in November 2017.

Drug treatments

There have been huge developments in the field of research and drug treatment in recent years; however not all of these treatments are suitable or possible for all children, young people and adults who have SMA. This is for different reasons for the different drugs. For example, it may be to do with safety limits based on clinical trials, or due to the decisions of UK regulatory authorities. These decisions are based on their assessments of the pharmaceutical company’s clinical trial and cost effectiveness evidence, as well submissions from clinicians and patient groups.

Nusinersen / SpinrazaTM

This drug, delivered by lumber puncture, was the first to have been licensed for the treatment of 5q SMA in the UK. It’s designed to modify the product of the SMN2 gene to produce more functional SMN protein.

See this page for more information about:

  • how it works, how it is given, and how often
  • the clinical trial results
  • who it is considered safe for, and who may have access in the UK.
     

Onasemnogene abeparvovec / ZolgensmaTM

This gene therapy treatment, delivered by injection into the bloodstream, is designed to address the genetic root cause of SMA and limit the progression of the condition by replacing the faulty or missing SMN1 gene.

See this page for more information about:

  • how it works, how it is given and how often 
  • the clinical trial results
  • who it is considered safe for, and who may have access in the UK.
     

Risdiplam / EvrysdiTM

This drug treatment, delivered orally, targets and encourages the SMN2 ‘back-up’ gene to produce a greater amount of functional SMN protein.

See this page for more information about:

  • how it works, how it is given and how often
  • the clinical trial results
  • who it is considered safe for, and who may have access in the UK. 

Research and further developments

There is still a considerable amount of research into SMA taking place around the world. This will continue to improve our understanding of the condition and will also help with the further development of effective management and treatments.

To keep up-to-date with the latest developments in research and drug treatments, visit this page.


Resources and Support

The International Standards of Care for Spinal Muscular Atrophy (2017) can be downloaded from here.

SMA UK

Phone: 01789 267 520
Email: supportservices@smauk.org.uk
Website: www.smauk.org.uk

We provide a free Support & Outreach Service for families and adults by email, phone, text or virtual meeting. When covid-safe, we can offer an outreach home visit. Our experienced team offers personalised support and information and is available to answer questions and talk things through. Though we don’t give medical advice, we can discuss support options with you.

We also support health, education and social care professionals.

If you're wondering about an aspect of life with SMA, we hope the Living With SMA area of our website will be a helpful starting point, giving you useful information and ideas. It builds on knowledge and advice from the SMA Community and SMA UK's Support Services Team. It covers a whole host of topics, including: health & wellbeing, equipment, homes, education, work, transport, leisure, holidays, financial, and emotional & social support: www.livingwithsma.org.uk
 

SMA UK’s monthly E-news keeps the community up-to-date and includes the latest research and treatment updates. You can sign up here.

Version 3
Author: SMA UK Information Production Team
Last full review: September 2020
Last updated: March 2022

Next full review due: September 2023
 

References

  1. A Guide to the 2017 International Standards of Care for SMA. Available at: http://smauk.org.uk/international-standards-of-care-for-sma (Accessed: 14th May 2021)
     
  2. Mercuri E et al. (2018) Diagnosis and management of spinal muscular atrophy: Part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord 28: 103-115.
     
  3. Finkel RS et al. (2018) Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord 28: 197-207.
     
  4. Finkel RS et al. (2017) ENMC SMA Workshop Study Group. 218th ENMC International Workshop: Revisiting the consensus on standards of care in SMA Naarden, The Netherlands, 19-21 February 2016. Neuromuscul Disord 27 (6):596-605.
     
  5. Wang CH et al. (2007) Consensus statement for standard of care in spinal muscular atrophyJ Child Neurol 22: 1027-1049.
     
  6. Farrar MA et al. (2013) Pathophysiological insights derived by natural history and motor function of spinal muscular atrophy. J Pediatrics 162: 155-159.
     
  7. Gusset N et al. (2021) Understanding European patient expectations towards current therapeutic development in spinal muscular atrophy. Neuromuscul Disord 31(5):419-430
     
  8. Zerres K et al. (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.
     
  9. Lunn MR & Wang CH (2008) Spinal muscular atrophy. Lancet, 371: 2120-2133.
     
  10. Lefebvre S et al. (1995) Identification and characterization of a spinal muscular atrophy-determining geneCell 80: 155-165.
     
  11. Mailman et al. (2002). Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med 4: 20-26.
     
  12. Lefebvre S et al. (1997). Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16: 265-269.
     
  13. Ruggiu, M et al. (2012) A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophyMol Cell Biol 32: 126-138.
     
  14. Tillmann R et al. (2018) Spinal Muscular Atrophy (SMA) type 1, a changing phenotype: implications for motor function and physiotherapy management from the Nusinersen Expanded Access Program (EAP). APCP Journal 9: 4-12.
     
  15. Verhaart IEC et al. (2017) Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy – a literature review. Orphanet J Rare Dis 12: 124.
     
  16. Verhaart IEC, et al. (2017) A multi-source approach to determine SMA incidence and research ready population. J Neurol 264: 1465-1473.
  17. Office of National Statistics (2021) Births in England and Wales: 2020. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/
    birthsdeathsandmarriages/livebirths/bulletins/
    birthsummarytablesenglandandwales/2020
    (Accessed 15th March 2022)

  18. National Records of Scotland (2020) Available at: National Records of Scotland (2020) List of Data Tables, Section 3 Births. Available at: https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/general-publications/vital-events-reference-tables/2020/list-of-data-tables#section3 (Accessed 15th March 2022)

  19. Northern Ireland Statistics and Research Agency (2021)  Registrar General Annual Report 2020 Births. Available at: https://www.nisra.gov.uk/publications/registrar-general-annual-report-2020-births (Accessed March 2022)

  20. Office for National Statistics (2021) Population estimates for the UK, England and Wales, Scotland and Northern Ireland: mid-2020. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/
    populationandmigration/populationestimates/bulletins/
    annualmidyearpopulationestimates/mid2020#the-uk-population-at-mid-2020
    (Accessed 15th March 2022)

  21. Public Health England (2019) Spinal Muscular Atrophy type 1: National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) data briefing. Available at: https://www.gov.uk/government/publications/spinal-muscular-atrophy-type-1-ncardrs-data-briefing/spinal-muscular-atrophy-type-1-ncardrs-data-briefing (Accessed: 15th March 2022)

 

We are grateful to the writers and reviewers who assist us in our information production. A list of who this includes may be requested from office@smauk.org.uk 

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 UK shall not be liable whatsoever for any damages incurred as a result of its use. SMA UK does not necessarily endorse the services provided by the organisations listed in our information sheets.

The information given in our publications is not intended to replace that provided by your healthcare team. Medical advice for any individual should always come from their own medical team.

If you have any feedback about this information, please do let us know at: office@smauk.org.uk