Spinal Muscular Atrophy (SMA)

What is spinal muscular atrophy?

Spinal muscular atrophy (SMA) represents a group of genetic (inherited) neuromuscular disorders that cause certain muscles to become weak and waste away (atrophy).

SMA involves the loss of a specific type of nerve cell in your spinal cord called lower motor neurons, or anterior horn cells. These cells control muscle movement. Without these motor neurons, muscles don’t receive the nerve signals that make them move.

The weakness in SMA tends to be more severe in the muscles that are close to the center of your body (proximal muscles) than in the muscles farther away from your body’s center (distal muscles). Muscle weakness tends to worsen with time.

Types of SMA

There are five subtypes of SMA. Healthcare providers classify them based on the age of onset, as well as the severity and life expectancy. The subtypes include:

• SMA type 0 (congenital SMA): This is a rare subtype that affects a fetus before birth. Pre-birth, there are typically decreased fetal movements. At birth, infants with type 0 have severe muscle weakness and typically go into respiratory failure. Death usually happens at birth or within the first month of life.
• SMA type 1 (severe SMA): About 60% of SMA cases are type 1 — also called Werdnig-Hoffman disease. Symptoms arise within the first six months of life and include limited head control and decreased muscle tone (hypotonia). Infants with type 1 SMA also have difficulty swallowing and breathing. Without breathing support, children with type 1 SMA die before their second birthday.
• SMA type 2 (intermediate SMA): Symptoms of type 2 SMA (also called Dubowitz disease) appear between six months and 18 months of life. Symptoms include hypotonia and worsening muscle weakness, which tends to affect their legs more than their arms. Children with type 2 SMA may be able to sit up but can’t walk. Around 70% of people with type 2 will survive until 25, with some surviving into their 30s. Respiratory issues are the major cause of death.
• SMA type 3 (mild): Symptoms of type 3 SMA (also called Kugelbert-Welander disease) appear after a child’s first 18 months of life. Type 3 symptoms include lower limb muscle weakness, leading to difficulty walking. People with type 3 MSA don’t tend to develop breathing issues, and it typically doesn’t affect life expectancy.
• SMA type 4 (adult): This is the mildest form of SMA. It doesn’t typically appear until after the age of 21. Muscle weakness symptoms progress slowly, so most people with type 4 remain mobile. It typically doesn’t affect life expectancy.

How common is SMA?

Although SMA is thought of as uncommon, it’s the second most common severe hereditary disease of infancy and childhood after cystic fibrosis. Researchers estimate that it affects between 1 in 6,000 to 1 in 11,000 live births. SMA is about twice as common in white and Asian people as it is in Black and Hispanic people.

What are the symptoms of SMA?

In general, the main symptom of SMA is muscle weakness — typically, in the muscles closest to the center of your body. But the symptoms vary based on the type.

Symptoms of SMA type 0 include:

• Decreased fetal movements.
• Arthrogryposis.
• Decreased muscle tone (hypotonia).
• Severe muscle weakness.
• Severe breathing issues.

Symptoms of SMA type 1 include:

• Limited head control.
• Hypotonia.
• Lack of reflexes (areflexia).
• Inability to sit without support.
• Abnormal breathing pattern and a bell-shaped chest.
• Difficulty swallowing, which can lead to growth issues (failure to thrive).
• Facial muscle weakness. This develops later on in the condition.

Symptoms of SMA type 2 include:

• Hypotonia and areflexia.
• Progressive muscle weakness that affects your child’s legs more than their arms.
• Scoliosis.
• Muscle weakness in your child’s chest, which can result in restrictive lung disease.
• Jerky movements in your child’s hands (polyminimyoclonus).
• Stiffening of your child’s jaw (mandible) joint due to bone fusion (ankylosis).
• Joint contractures.

Symptoms of SMA type 3 mainly involve progressive muscle weakness that affects your child’s legs more than their arms.

The main symptom of SMA type 4 is mild leg weakness.

What causes spinal muscular atrophy (SMA)?

SMA is a genetic condition, which means you inherit genes from your biological parents that cause the condition.

Mutations (changes) in the SMN1 (survivor motor neuron 1) gene cause all types of spinal muscular atrophy. The number of copies that you have of the SMN2 gene alters the severity of the condition.

A healthy SMN1 gene produces SMN protein. Motor neurons need this protein to survive and function properly. If you have SMA, your body doesn’t make enough SMN protein, so your motor neurons shrink and die. As a result, your brain can’t control voluntary movements, especially motion in your head, neck, chest and legs.

The SMN2 gene also produces a small amount of SMN protein. A person may have up to eight copies of an SMN2 gene. Having multiple copies of the SMN2 gene typically leads to less severe SMA symptoms because the extra genes make up for the missing SMN1 protein.

Inheritance pattern of SMA

You inherit SMA in an autosomal recessive pattern, which means both of your biological parents pass on mutations in the SMN1 gene. In most cases, the biological parents of someone with an autosomal recessive condition each carry one copy of the mutated gene. But these carriers typically don’t have symptoms of the condition. In the general population, mutations of the SMN1 gene are common. Among white people, 1 in 50 may be a carrier.

In rare cases, you may inherit an SMN1 gene mutation from one parent and acquire a new mutation in the other copy of the gene during embryonic development.

How is SMA diagnosed?

To start the diagnosis process, a healthcare provider will ask about your or your child’s medical history and symptoms. They’ll then do physical and neurological exams.

If your provider suspects SMA, the main test that can confirm it is genetic testing. This blood test can confirm 95% of SMA cases by identifying problems with the SMN1 gene. Each of the 50 U.S. states now routinely screens newborns for SMA.

Some SMA symptoms resemble those of other neuromuscular disorders, like muscular dystrophy. If your provider doesn’t immediately suspect SMA, they may recommend any of the following tests to find the cause:

• Creatine kinase blood test: Deteriorating muscles release this enzyme into your bloodstream. But the levels are typically normal with SMA, unlike with other neuromuscular disorders.
• Electromyogram (EMG) and nerve conduction study: These tests measure the electrical activity of your muscles and nerves.
• Muscle biopsy: Rarely, your provider may request a muscle biopsy. This procedure involves removing a small amount of your muscle tissue and sending it to a lab for examination.

Can spinal muscular atrophy be diagnosed during pregnancy?

If you’re pregnant and have a family history of SMA, prenatal genetic testing may be able to check if the developing fetus has the condition. Prenatal tests for SMA include:

• Amniocentesis: During amniocentesis, your healthcare provider inserts a thin needle into your belly to draw out a small amount of amniotic fluid. A pathologist checks the sample for SMA. This test happens after the 14th week of pregnancy.
• Chorionic villus sampling (CVS): Your provider removes a small tissue sample from the placenta through your cervix or belly. A pathologist checks the sample for SMA. CVS can take place as early as the 10th week of pregnancy.

What is the treatment for SMA?

Unfortunately, there isn’t a cure for SMA. Treatment for SMA mainly seeks to manage symptoms and prevent complications. Symptom management therapies may include:

• Physical therapy, which can help improve posture, prevent joint immobility and slow muscle weakness.
• Occupational therapy, which can improve your ability to perform daily tasks.
• Assistive devices, like orthopaedic braces, crutches, walkers and wheelchairs.
• Therapy for speech and swallowing difficulties.
• A feeding tube if swallowing is too difficult and/or dangerous.
• Assisted ventilation for breathing issues.

Medications for SMA

Between 2016 and 2020, the U.S. Food and Drug Administration (FDA) approved treatments that can significantly improve the course of SMA. They include:

• Disease-modifying therapy: These medications stimulate the production of SMN2 protein. The FDA has approved Nusinersen (Spinraza®) for both children and adults. A healthcare provider injects the medication into the space around your spinal canal. A different medication, risdiplam (Evrysdi®), helps those with SMA who are 2 months and older. You take risdiplam daily by mouth (orally).
• Gene replacement therapy: Children younger than 2 may benefit from a one-time intravenous (IV) infusion of a medication called onasemnogene abeparvovec-xioi (Zolgensma®). This therapy replaces a missing or faulty SMN1 gene with a functioning gene.

These newer treatments may be particularly effective if started early, even before symptoms of SMA appear. Given the availability of these treatments, there’s now routine screening of newborns for SMA in the United States.

Your child may also be able to participate in a clinical trial for SMA. Talk with your child’s healthcare team to see if this is an option.

Can I prevent SMA?

SMA is an inherited condition, so it’s not typically preventable. But genetic testing can help you understand your odds of having a biological child with SMA.

Carrier testing for SMA is available using a genetic test. If you or your partner carry the mutated gene that causes SMA, a genetic counselor can explain the chances of your child having SMA or being a carrier.

You may be able to take steps before pregnancy to lower the risk of passing on SMA. A process called preimplantation genetic diagnosis (PGD) identifies embryos that don’t have the mutated gene. Your healthcare provider implants healthy embryos during in vitro fertilization (IVF).

What is the prognosis for someone with SMA?

The prognosis (outlook) for someone with SMA varies based on the subtype. Your healthcare team can give you a better idea of what to expect based on your or your child’s situation.

Complications of SMA

Over time, children with SMA experience progressive muscle weakness and loss of muscle control. Potential complications include:

• Bone fractures, hip dislocation and scoliosis.
• Malnutrition and dehydration due to problems eating and swallowing.
• Chest infections, like aspiration pneumonia, due to swallowing issues.
• Weak lungs and breathing problems that may require breathing support (ventilation).

People with SMA are also prone to metabolic acidosis, especially during periods of illness or fasting. Researchers aren’t sure why this happens.

What is the life expectancy of someone with SMA?

The life expectancy of someone with SMA largely depends on the type:

• SMA type 0 results in death at birth or within one month of life.
• SMA type 1 often results in death by the age of 2 without breathing support.
• Life expectancy for SMA type 2 varies but is usually between 20 and 40 years.
• SMA types 3 and 4 typically don’t affect life expectancy.

It’s important to note that disease-modifying and gene replacement therapies have been proven to substantially improve survival in SMA type 1. Your healthcare team will be able to give you a better idea of what to expect.

How do I take care of my child with SMA?

If your child has SMA, it’s important to advocate for them to ensure they get the best medical care and as much access to therapy as possible. Advocating for care can help them have the best possible quality of life.

You and your family may also want to consider joining a support group to meet others who can relate to your experiences.

What questions should I ask my healthcare provider?

If you or your child have SMA, it may be helpful to ask your healthcare provider the following questions:

• What type of SMA do I or my child have?
• What’s the prognosis for this type of SMA?
• What’s the best treatment for this type of SMA?
• What are the treatment risks and side effects?
• Are other members of my family at risk for getting SMA? If so, should we get genetic tests?
• What type of ongoing care will I or my child need?
• What signs of complications should I look out for?