Spinal Muscular Atrophy (SMA)
What is spinal muscular atrophy (SMA)?
Spinal muscular atrophy (SMA) is a genetic (inherited) neuromuscular disease that causes muscles to become weak and waste away. People with SMA lose a specific type of nerve cell in the spinal cord (called motor neurons) that control muscle movement. Without these motor neurons, muscles don’t receive nerve signals that make muscles move. The word atrophy is a medical term that means smaller. With SMA, certain muscles become smaller and weaker due to lack of use.
How common is spinal muscular atrophy?
Approximately 10,000 to 25,000 children and adults are living with SMA in the United States. It’s a rare disease that affects one out of 6,000 to 10,000 children.
Who might get spinal muscular atrophy?
A person with SMA inherits two copies of a missing or faulty (mutated) survival motor neuron 1 (SMN1) gene. One faulty gene comes from the mother and the other comes from the father. An adult can have a single copy of the defective gene that causes SMA and not know it.
About six million Americans (1 in 50) carry the mutated SMN1 gene. These carriers have one healthy SMN1 gene and one missing or defective SMN1 gene. Carriers don’t develop SMA. There's a 1 in 4 chance that two carriers will have a child with SMA.
What are the types of spinal muscular atrophy?
There are four primary types of SMA:
- Type 1 (severe): About 60% of people with SMA have type 1 , also called Werdnig-Hoffman disease. Symptoms appear at birth or within an infant’s first six months of life. Infants with type 1 SMA have difficulty swallowing and sucking. They don’t meet typical milestones like holding up their heads or sitting. As muscles continue to weaken, children become more prone to respiratory infections and collapsed lungs (pneumothorax). Most children with type 1 SMA die before their second birthday.
- Type 2 (intermediate): Symptoms of type 2 SMA (also called Dubowitz disease) appear when a child is between six months and 18 months old. This type tends to affect the lower limbs. Children with type 2 SMA may be able to sit up but can’t walk. Most children with type 2 SMA live into adulthood.
- Type 3 (mild): Symptoms of type 3 SMA (also called Kugelbert-Welander or juvenile-onset SMA) appear after a child’s first 18 months of life. Some people with type 3 don’t have signs of disease until early adulthood. Type 3 symptoms include mild muscle weakness, difficulty walking and frequent respiratory infections. Over time, symptoms can affect the ability to walk or stand. Type 3 SMA doesn’t significantly shorten life expectancy.
- Type 4 (adult): The rare adult form of SMA doesn’t typically appear until the mid-30s. Muscle weakness symptoms progress slowly, so most people with type 4 remain mobile and live full lives.
Symptoms and Causes
What causes spinal muscular atrophy?
People with SMA are either missing part of the SMN1 gene or have a changed (mutated) gene. A healthy SMN1 gene produces SMN protein. Motor neurons need this protein to survive and function properly.
People with SMA don’t make enough SMN protein, and so the motor neurons shrink and die. As a result, the brain can’t control voluntary movements, especially motion in the head, neck, arms and legs.
People also have SMN2 genes that produce 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. Rarely, non-SMN gene mutations (non-chromosome 5) cause SMA.
What are the symptoms of spinal muscular atrophy?
SMA symptoms vary depending on the type. In general, people with SMA experience a progressive loss of muscle control, movement and strength. Muscle loss gets worse with age. The disease tends to severely affect the muscles closest to the torso and neck. Some people with SMA never walk, sit or stand. Others gradually lose their ability to do these actions.
Diagnosis and Tests
How is spinal muscular atrophy diagnosed?
Some SMA symptoms resemble those resulting from neuromuscular disorders like muscular dystrophy. To find the cause of symptoms, your healthcare provider will perform a physical exam and get a medical history. Your physician may also order one or more of these tests to diagnose SMA:
- Blood test: An enzyme and protein blood test can check for high levels of creatine kinase. Deteriorating muscles release this enzyme into the bloodstream.
- Genetic test: This blood test identifies problems with the SMN1 gene. As a diagnostic tool, a genetic test is 95% effective at finding the altered SMN1 gene. Some states test for SMA as part of routine newborn screenings.
- Nerve conduction test: An electromyogram (EMG) measures the electrical activity of nerves muscles and nerves.
- Muscle biopsy: Rarely, a physician may perform a muscle biopsy. This procedure involves removing a small amount of muscle tissue and sending it to a lab for examination. A biopsy can show atrophy, or loss of muscle.
Can spinal muscular atrophy be diagnosed during pregnancy?
If you’re pregnant and have a family history of SMA, prenatal tests can determine if your unborn baby has the disease. These tests slightly increase the risk of miscarriage or pregnancy loss. Prenatal tests for SMA include:
- Amniocentesis: During amniocentesis, your obstetrician inserts a thin needle into your belly to draw out a small amount of fluid from the amniotic sac. A lab specialist (pathologist) checks the fluid for SMA. This test takes place after the 14th week of pregnancy.
- Chorionic villus sampling (CVS): Your obstetrician removes a small tissue sample from the placenta through the mother’s cervix or stomach. A pathologist checks the sample for SMA. CVS can take place as early as the 10th week of pregnancy.
Management and Treatment
How is spinal muscular atrophy managed or treated?
There isn’t a cure for SMA. Treatments depend upon the type of SMA and symptoms. Many people with SMA benefit from physical and occupational therapy and assistive devices, such as orthopaedic braces, crutches, walkers and wheelchairs.
These treatments may also help:
- Disease-modifying therapy: These drugs stimulate production of SMN protein. Nusinersen (Spinraza®) is for children ages 2 to 12. Your provider injects the drug into the space around the spinal canal. A different medication, risdaplam (Evrysdi®), helps adults and children older than two months. People take risdaplam daily by mouth (orally).
- Gene replacement therapy: Children younger than two may benefit from a one-time intravenous (IV) infusion of a drug called onasemnogene abeparvovec-xioi (Zolgensma®). This therapy replaces a missing or faulty SMN1 gene with a functioning gene.
What are the complications of spinal muscular atrophy?
Over time, people with SMA experience progressive muscle weakness and loss of muscle control. Potential complications include:
How can I prevent spinal muscular atrophy?
SMA is an inherited disease. If you or your partner carries 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 doctor implants healthy embryos during in vitro fertilization (IVF). PGD ensures your child will have two healthy SMN1 genes and not get SMA.
Outlook / Prognosis
What is the prognosis (outlook) for people with spinal muscular atrophy?
The quality of life and life expectancy for people with SMA varies depending on the type. Infants with type 1 SMA usually die before their second birthday. Children with type 2 or type 3 SMA may live full lives depending on the severity of symptoms. People who develop SMA during adulthood (type 4) often remain active and enjoy a normal life expectancy.
When should I call the doctor?
You should call your doctor if someone with SMA experiences:
- Difficulty breathing, cough or other signs of pneumonia.
- Nausea, vomiting or diarrhea.
- Signs of dehydration, such as dark-colored urine or extreme fatigue.
What questions should I ask my doctor?
You may want to ask:
- How did I or my child get SMA?
- What type of SMA do I or my child have?
- What’s the prognosis for this type of SMA?
- What is the best treatment for this type of SMA?
- What are the treatment risks and side effects?
- Are other family members at risk for getting SMA? If so, should we get genetic tests?
- What type of ongoing care will I or my child need?
- Should I look out for signs of complications?
A note from Cleveland Clinic
SMA is a genetic neuromuscular disease that can significantly affect quality of life and life expectancy. It’s a progressive disease that gets worse over time. Symptoms may be present at birth (type 1), or develop during childhood (type 2 or 3) or in adulthood (type 4). Newer disease-modifying and gene replacement therapies offer promise. It’s possible to carry the gene that causes SMA and not know it. If SMA runs in your family, talk to your doctor about ways to lower your future baby’s chance of getting SMA.