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What is Spinal Muscular Atrophy and what causes it?

Spinal Muscular Atrophy (SMA) is a genetic condition. This inherited condition affects the motor neurons in the spinal cord which control the muscle movement of the body, including the muscles for head control, arm and leg movement, and the actions of breathing, coughing and swallowing. As SMA progresses coughing becomes more difficult, and breathing becomes laboured.

SMA Facts

  • SMA is the childhood version of Motor Neurone disease.
  • 1 in 35 people in Australia unknowingly carry the faulty SMA gene. Being a carrier does not mean you are affected by the condition.
  • One in 10,000 live births in Australia are
    affected by SMA.
  • 60-70% of all SMA patients have the
    most severe form (Type 1).
  • SMA is a physical condition only. Children
    with SMA have reduced movement.
  • There is no known cure for Spinal
    Muscular Atrophy, however, with there are
    three treatment options for children and
    two treatment options for adults with SMA in Australia.
  • Untreated Babies (Type 1) don’t often reach milestones like sitting or rolling in early infancy, have hypotonia (floppiness), progressive weakness and loss of motor function.
  • Initially, babies born with SMA appear perfectly normal in every way except they become extremely weak. They are bright, alert, interested in people and what’s going on around them. They enjoy music and being played with – just like other babies.
  • SMA children’s intelligence is unaffected. Many people with SMA have above average intelligence. Children go to mainstream schools, adults work (i.e: graphic design, lawyer) and even have children themselves.
  • A person is born when BOTH parents are carriers of this gene, neither parent is to blame. There is a 1 in 4 chance of this couple having future babies with SMA.
  • Children with SMA can be more susceptible to catching colds so washing hands before having contact is very important. Avoid visits by anyone suffering a cough / cold or anything
    contagious.
  • Infants / Children / Adults diagnosed with Type 3 and 4 have a full life expectancy, but mobility and dexterity are compromised.
  • Those affected by infantile and childhood SMA may rely on a wheelchair for mobility, develop scoliosis, a curved spine, and require surgical intervention.
  • SMA does restrict people’s ability to care for one’s self but usually someone with SMA will require assistance with daily living activities.
  • SMA, historically (untreated) was the number one genetic cause of infant mortality in the world.

Estimates show that SMA occurs in 1:10,000 live births and untreated is the number one genetic cause of death for children under the age of two.

How is SMA inherited?

SMA is a recessive disorder caused by a deficiency in the survival motor neuron (SMN) protein. The SMN protein is encoded by the SMN1 gene.

This means that individuals with SMA have inherited two non-working copies of the SMN1 gene, one from each parent. Parents of children who have SMA are called carriers because they have only one non-working copy and do not have SMA.

Parents of SMA children are usually unaware they carry the change in their SMN1 genes and often have not heard of SMA until their child has been diagnosed. Two carriers will have a one in four (25%) chance of having an affected child in each pregnancy, a one in two (50%) chance of a child who is unaffected carrier, and one in four (25%) chance of a child who does not have an SMA and is not a carrier.

In rare cases, about 2% SMA is not inherited, but is due to a spontaneous error (de novo), in which case parents do not carry the SMA causing gene.

Individuals with SMA have inherited two non-working copies of this gene, one from each parent. Two carriers of the faulty SMA gene will have a:

  • 25% chance of having a child in each pregnancy affected by SMA,
  • 50% chance of a child who is an unaffected carrier, and
  • 25% chance of a child who does not have SMA and is not a carrier.

How many types of Spinal Muscular Atrophy are there?

SMA is a very complex condition and each child, and each set of parents face their own unique journey and their own unique decisions, as SMA affects each person so very differently. It is important to care for the person in a way that best meets their specific needs and those of their family.

There are many types of SMA that are caused by changes in the same gene. Current classification of five types is based on age of onset and achievement of motor milestones at the initial assessment, but overlap between these exists, so considering SMA as a spectrum is more correct.

  • Type 0 (prenatal onset or arthrogryposis multiplex congenital SMA) – Symptoms are evident at birth
  • Type 1 (Infantile SMA or Werdnig-Hoffman disease) – Symptoms can develop during the first few weeks of life, usually 3 – 9 months. Child never sits unsupported.
  • Type 2 (Intermediate SMA or chronic childhood SMA) – Symptoms usually appear around 7 – 19 months of age. Child never pulls to stand or walks.
  • Type 3 (Juvenile SMA or Kugelberg-Welander disease) – Symptoms appear usually by 2 – 7 years of age. Child may learn to walk, however they will gradually lose this skill.
  • Type 4 (Adult onset Spinal Muscular Atrophy) – Symptoms are mild and can appear from puberty to late adulthood.
  • SMARD (SMA with respiratory distress) – It is non-responsive to treatment leading to early death.

*SMA Type 0 should not be confused with SMARD1, which may have very similar symptoms and course but has a different genetic cause than SMA.

The predictive value of the classical classification of SMA, which is solely based on motor assessment at initial presentation is now very limited and not very practical for newly diagnosed patients commencing treatment. Updated clinical guidelines for management now recommend classification as nonsitters, sitters and walkers to recognise current functional status and therapy response.

Are there treatments for Spinal Muscular Atrophy?

Up until 6 years ago there was no treatment for SMA. The global SMA community has seen the landscape change rapidly with not one but three treatments now available in Australia

SPINRAZA (by Biogen) was the first available treatment in Australia, approved by the Pharmaceutical Benefit Scheme (PBS) in May 2018 for those with Type 1, 2 and 3 under the age of 19 years. It is delivered through a lumber puncture. Spinraza works on a backup gene called survival motor neuron 2 (SMN2) that makes a small amount of SMN protein (but not enough) to increase its production of the SMN protein. On 1 August 2022, Spinraza became the first reimbursed treatment to be made available on the PBS for SMA adults in Australia.

EVEYSDI (Risdiplam) (by Roche) became the second treatment available to SMA children in Australia when it was listed on the PBS in August 2021. Eveysdi is an oral treatment, taken on a daily basis, that also targets the SMN2 gene to increase SMN protein production. In October 2023, Eveysdi’s listing on the PBS was extended, providing the adult SMA community two treatment options.

ZOLGENSMA (by AveXis, a Novartis company) is Australia’s first gene therapy treatment, and the third treatment option available on the PBS (May 2022) for children less than 2 years of age. The gene replacement therapy the missing or non-working survival motor neuron 1 (SMN1) gene with new working copy of a human SMN1 gene. It is delivered inside a harmless virus, called adenoassociated virus type 9 (AAV9) as a single intravenous infusion.

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