What is spinal muscular atrophy (SMA)?
Spinal muscular atrophy (SMA) is a genetic condition that leads to muscle weakness that worsens over time. SMA is caused by a loss of motor neurons. These special nerve cells control muscles. The nerve cells are found in the spinal cord and part of the brain.
SMA affects the muscles that help us speak, breathe, and swallow. It also affects muscles that help us perform daily activities such as walking. When these muscles do not receive signals from the nerve cells, they begin to waste away (atrophy).
What causes SMA?
Genetic diseases are caused by changes in a person’s DNA, or genetic code. SMA involves a change in a small part of DNA called the SMN1 gene. This gene tells the body to make the survival motor neuron (SMN) protein. The SMN protein is crucial for normal motor neuron function and survival.
People with the classic form of SMA have two missing or faulty copies of the SMN1 gene. This causes the nerve cells that control muscle movement to fail to function. Over time, these nerve cells die. Their death leads to muscle atrophy. Changes in a similar gene called SMN2 provide a small amount of the SMN protein which can affect disease severity.
In most SMA cases both parents pass on the genetic changes. This means both parents carry a faulty gene but do not have any SMA symptoms. A test can show whether someone carries one faulty copy of SMN1. It helps show if a person has a risk of having a child with SMA.
What are the types of SMA?
There are 5 main types of SMA. They are grouped based on when symptoms begin. If symptoms begin in infancy, the disease may progress more quickly and be more severe. These children may also have shorter lives.
- SMA type 0 (also called prenatal-onset SMA): Infants born with this rare and severe type of SMA have very weak muscle tone and poor strength at birth. They never learn to sit on their own. The babies have problems breathing and eating and may have heart defects. Infants with SMA type 0 often do not move much, even in the womb. Unfortunately, they do not survive beyond 1 year.
- SMA type 1 (Also called Werdnig-Hoffmann disease, or early infantile-onset SMA): This type is usually diagnosed by 6 months. It is the most common form of SMA. Before recent treatments for SMA, many of these babies needed feeding tubes or help with breathing. They could not roll over or sit on their own. These babies usually do not live more than 2 years without major supportive care.
- SMA type 2 (Also called Dubowitz disease, or late infantile-onset SMA): This type is typically diagnosed between 6 and 24 months of age. These children can sit on their own but fail to walk. As they get older, they may lose the ability to sit. Children with SMA type 2 may also develop scoliosis (a curved spine). They can have problems eating and breathing. They usually live into their 20s or 30s.
- SMA type 3 (Also called Kugelberg-Welander disease or juvenile SMA): This mild form of SMA develops in childhood usually after 18 months of age. These children can learn to walk. Later in life they may lose this ability and need a wheelchair. Life expectancy is normal.
- SMA type 4: This rare form of SMA appears in young adults. Symptoms are usually mild. People with this type of SMA may have fatigue and weak muscles. People with SMA type 4 usually do not have feeding or breathing issues.
Other rare types of SMA are caused by defects in other genes (not connected to SMN1). These include:
- SMA respiratory distress (SMARD): This form of SMA causes severe breathing problems and weak muscles. SMARD usually occurs in infants.
- Distal SMA: This form of SMA causes weakness in the hands and feet. Distal SMA usually occurs in older children.
- Kennedy’s disease: This form of SMA affects adult males. Symptoms include problems swallowing and muscle weakness that gets worse over time.
What are the symptoms of SMA?
Symptoms vary based on when SMA first appears. In general, if SMA symptoms present earlier in life, then the disease will be more severe and progress more rapidly. The symptoms tend to get worse without treatment. SMA is not known to affect a child’s brain, emotions, or ability to learn.
The most common symptoms in infants:
- Weak muscles and low muscle tone. This is known as “floppy baby” hypotonia.
- Failure to develop basic skills, such as rolling over, sitting up, or walking
- Poor arm and hand function
- Limited head control
- Trouble breathing
- Problems feeding, swallowing, and speaking
Symptoms in children:
- Weak muscles and limited muscle development
- Problems sitting or walking, which get worse over time
- Tight joints (contractures) and curved spine (scoliosis) with poor posture
- Respiratory infections often and sometimes severe
- Problems eating and swallowing. These issues can lead to pneumonia and poor weight gain.
- A soft nasal voice
How common is SMA?
SMA affects 1 out of every 8,000 to 10,000 people. It can appear at any stage of life, but it is more common in infants and children. About 1 in 40 people may carry the gene that causes SMA.
How is genetic testing for SMA done?
Many US states offer newborn screening for SMA. This blood test can find SMA, which makes it possible to begin treatment before symptoms become apparent.
A first-level genetic test can find 95% of SMA cases. A second-level test can find the remaining 5%. A carrier test can also show if a person carries the SMN1 gene change and could pass it on to their children.
Other tests that are not done as often:
- Nerve conduction velocity study: Small electric impulses are applied to a nerve and measure how well the muscle is activated.
- Electromyography (EMG): Small needles put into the skin measure the health of muscles and nerve cells.
- Muscle biopsy: A bit of muscle tissue is removed and studied for SMA signs.
What treatments are available for SMA?
We are learning more about SMA and how to treat it. New therapies have greatly improved outcomes for many children with SMA. Research and clinical trials to develop and test new therapies are ongoing.
Treatment options depend on the child’s age and diagnosis. These may include:
- SMN-enhancing drugs: These therapies may stop or slow how fast SMA progresses. The drugs may improve muscle function. For best results, treatment should begin as soon as possible. Approved medicines:
- Nusinersen (brand name Spinraza, approved in the US in 2016): It works by causing the SMN2 gene to make more SMN protein. The drug can be used to treat all ages. A clinical trial is testing whether using a higher nusinersen dose is safe and works well. This drug is injected into the spinal fluid every 4 months.
- Risdiplam (brand name Evrysdi, approved in the US in 2020): It works by causing the SMN2 gene to make more SMN protein. It can be used for children older than 2 months and in adults. This drug is taken by mouth daily.
- Onasemnogene abeparvovec (brand name Zolgensma, approved in the US in 2019): This gene therapy replaces the missing or faulty SMN1 gene with a normal copy. It can be used for children up to 2 years old in the US. This drug is given once by IV infusion.
- Muscle drugs: Several medicines that target the muscles and nerves are in clinical trials. These therapies might treat SMA but need more testing.
Other treatments that can help with SMA symptoms:
- Occupational therapy – to address fine motor skills and help with daily living activities
- Physical therapy – to improve range of motion, teach proper exercise and positioning, get the most from muscle function, and provide adaptive equipment.
- Respiratory therapy – to help with breathing and lung function
- Speech therapy – to help with speech and swallowing problems
- Assistive devices – including braces (orthotics), wheelchairs, and other devices to help with movement and independence
What are the survival rates for SMA?
Life expectancy depends on the type of SMA. The later the symptom onset, the fewer issues a child or adult is likely to have and the longer they are expected to live.
Treatments approved in the last several years can greatly improve the quality of life and life expectancy for many children with SMA. New therapies, if given early enough, can make it possible for babies to reach developmental milestones. If given before symptoms begin, a cure may be possible.
Why choose St. Jude for your child’s SMA treatment?
- We have expanded our focus on neurologic disorders by creating the Center for Experimental Neurotherapeutics. The center focuses on research and treatment of pediatric neurologic disorders.
- Richard S. Finkel, MD, leads the Center for Experimental Neurotherapeutics. He has 30 years of experience researching and treating SMA and other neurologic disorders. He was one of the experts who led the development of Spinraza, the first successful treatment for SMA, as well as Zolgensma and Evrysdi.
- St. Jude has a close relationship with two other Memphis institutions, Le Bonheur Children's Hospital and the University of Tennessee Health Science Center. We are partnering to create a Neuroscience Research Consortium. This group investigates treatments for children with severe neuromuscular diseases and other neurologic disorders.
- St. Jude is one of 6 sites that make up the Pediatric Neuromuscular Clinical Research Network. These sites work together to expand treatments, increase clinical trials, and promote newborn screening.
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