Spinal muscular atrophy is a group of genetic disorders in which a person cannot control the movement of their muscles due to a loss of nerve cells in the spinal cord and brain stem. It is a neurological condition and a type of motor neuron disease.
Spinal muscular atrophy (SMA) causes muscle wasting and weakness. It can be difficult for a person with SMA to stand, walk, control their head movements, and even, in some cases, breathe and swallow. Some types of SMA are present from birth, but others appear later in life. Some types affect life expectancy.
SMA affects one in every 8,000–10,000 people around the world, according to Genetics Home Reference.
There is no cure for SMA, but new drugs, such as nusinersen (Spinraza) and onasemnogene abeparvovec-xioi (Zolgensma), may slow its progress.
There are different types of SMA. They vary in terms of when symptoms start to appear and how they affect life expectancy and the quality of life.
The National Institute of Neurological Disorders and Stroke describe four types:
SMA type I
SMA type 1, or Werdnig-Hoffmann disease, is a serious condition that usually appears before the age of 6 months. A child may be born with breathing problems, which can be fatal within a year without treatment.
Symptoms include muscle weakness and twitching, a lack of ability to move the limbs, difficulty feeding, and, in time, a curvature of the spine. With newer treatments, such as disease modifying therapies (DMTs), some children with SMA type 1 can now learn to sit or walk.
A doctor may detect SMA type 1 before birth, as tests may show low levels of fetal movement during the final months of pregnancy. If not, it will become evident within the first few months of life.
SMA type 2
Symptoms of SMA type 2 usually appear at the age of 6–18 months. The infant may learn to sit, but they will never be able to stand or walk. In some cases, without treatment, the individual may lose their ability to sit.
Life expectancy depends on whether breathing problems are present. Most people with SMA type 2 survive into adolescence or young adulthood. Treatment with DMTs can help.
SMA type 3
SMA type 3, or Kugelberg-Welander disease, appears after the age of 18 months. The individual may have scoliosis or contractures, a shortening of the muscles or tendons, which can prevent the joints from moving freely.
Most people will continue to be able to walk, but they may have an unusual gait and experience difficulty running, climbing steps, or rising from a chair. There may also be a slight tremor of the fingers. Complications include a higher risk of respiratory infections.
With appropriate treatment, including with DMTs, a person can have a normal life expectancy.
Adult SMA, or SMA type 4, is rare. It begins after the age of 21 years. The person will have mild to moderate proximal weakness, which means that the condition affects the muscles closest to the center of the body.
It will not usually affect life expectancy.
The symptoms of SMA depend on its type and severity, as well as the age at which it develops.
Common symptoms include:
- muscle weakness and twitching
- difficulty breathing and swallowing
- changes in the shape of the limbs, spine, and chest due to muscle weakness
- difficulty standing, walking, and possibly sitting
At birth, infants with SMA type 1 have weak muscles, minimal muscle tone, and feeding and breathing problems. With SMA type 3, symptoms may not appear until the second year of life.
In all of its forms, the main features of SMA are muscle weakness and muscle wasting. These occur because the nerves that control movement, called motor neurons, are unable to give the muscles the signal to contract. The weakness tends to affect the muscles that are closer to the center of the body.
Motor neurons normally send these signals from the spinal cord to the muscles via the motor neuron’s axon. In SMA, either the motor neuron or the axon itself does not work or stops working.
SMA is a degenerative disease, and the symptoms tend to worsen over time.
Many of the changes are not strictly symptoms of SMA but complications of the resulting muscle weakness.
Therapy can partly lessen these issues.
SMA happens when motor neurons in the spinal cord and the brain stem either do not work or stop working because of changes in genes known as survival motor neuron 1 (SMN1) and SMN2.
Motor neurons are the nerve cells that control movement.
The SMN1 and SMN2 genes give instructions for creating the protein that is necessary for motor neurons to function.
A problem with SMN1 will lead to SMA, while an issue with SMN2 will affect the type and severity of SMA.
One in 40–60 adults have a genetic problem that can lead to SMA.
A person can only have SMA if both of their parents have a problem with this gene. However, even if both parents have this fault, there is only a 1 in 4 chance that the child will inherit it.
Diagnosis usually starts when parents or caregivers notice symptoms of SMA in a child.
A doctor will carry out a detailed medical history, a family history, and a physical exam. They will see if the muscles are floppy or flaccid, checking for deep tendon reflexes and any twitching of the tongue muscle.
Tests for diagnosing SMA may include:
- blood tests
- a muscle biopsy
- genetic tests amniocentesis or chorionic villus sampling during gestation
- electromyography (EMG)
EMG can assess the health of the muscles and the nerve cells, or motor neurons, that control them. Amniocentesis or chorionic villus sampling can allow the doctor to evaluate the fetus in the womb.
Some states recommend routine genetic screening for SMA at birth. Detecting the condition at this stage may allow for treatment before symptoms appear.
There is currently no cure for SMA and no way to prevent it, as it is an inherited condition. However, treatment can help a person live a full life.
DMTs can help reduce the severity of symptoms and improve the outlook for people with some types of SMA.
The Food and Drug Administration (FDA) have approved two drugs for SMA, and there are more in the pipeline.
This drug can treat all types of SMA. A doctor will inject four initial doses over about 2 months, followed by a maintenance dose every 4 months.
It belongs to a class of drugs called antisense oligonucleotides (ASOs), which aim to target the underlying problem by influencing the production of RNA.
Spinraza appears to slow the progression of SMA, and it may reduce muscle weakness, but its effectiveness might vary between individuals.
This medication is a type of gene therapy for treating infants aged under 2 years. A doctor will give it as an infusion in a single dose.
Both drugs can have adverse effects, and Zolgensma carries a boxed warning.
Researchers are working on other treatment options, such as gene replacement therapy and the use of stem cells to replace damaged motor neurons.
Assistive devices and therapy
Various types of assistive device can improve a person’s life expectancy and quality of life with SMA.
Assistive technology — which includes ventilators, powered wheelchairs, and modified access to computers — are enabling individuals with SMA to live longer, be more active, and participate more in the community.
Physical therapy is also part of the treatment. Options include water therapy and wheelchair sports.
SMA is a genetic condition that can affect children or adults, depending on the type.
A person’s outlook will depend on the severity of the symptoms. Infants with severe SMA may experience respiratory disease because the muscles that support breathing are weak. This complication can be fatal in some cases.
Many people with milder forms of SMA can expect to live as long as a person without SMA, although some may need extensive medical support.
It is not possible to prevent SMA, but medication, physical therapy, and other strategies can help a person live a full and active life.
As researchers learn more about SMA, new and experimental treatment options are showing promise for treating, preventing, or even curing the condition in the future.
People with a family history of SMA who are planning to start a family may wish to seek genetic counseling first.
My sister has just had a baby who seems healthy but has screened positive for SMA. What can she expect to happen?