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.

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.

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.

symptoms

SMA symptoms cover a broad spectrum, ranging from mild to severe.

The primary symptom of chromosome 5-related (SMN-related) SMA is weakness of the voluntary muscles. The muscles most affected are those closest to the center of the body, such as those of the shoulders, hips, thighs, and upper back. The lower limbs seem to be affected more than the upper limbs, and deep tendon reflexes are decreased.4

Special complications occur if the muscles used for breathing and swallowing are affected, resulting in abnormalities in these functions. If the muscles of the back weaken, spinal curvatures can develop.

There's a great deal of variation in the age of onset and level of motor function achieved in chromosome 5-related SMA. These are roughly correlated with how much functional SMN protein is present in the motor neurons, which in turn correlates with how many copies of SMN2 genes a person has. Sensory, mental, and emotional functioning are entirely normal in chromosome-5 SMA.

Some forms of SMA are not linked to chromosome 5 or SMN deficiency. These forms vary greatly in severity and in the muscles most affected. While most forms, like the chromosome 5-related form, affect mostly the proximal muscles, other forms exist that affect mostly the distal muscles (those farther away from the body’s center) — at least in the beginning.

SMA linked to chromosome 5 (SMN-related), types 0-4

In spinal muscular atrophy (SMA) types 0 through 4, symptoms vary on a continuum from severe to mild based on how much functional SMN protein there is in the nerve cells called motor neurons. (“SMN” stands for survival of motor neuron.) The more SMN protein there is, the later in life symptoms begin and the milder the course of the disease. The number of copies of SMN2 genes, which can offset malfunctioning SMN1 genes, determines SMA’s severity and the patient’s age of onset.

Mothers of children affected by SMA type 0 may report a decrease in fetal movement in late pregnancy and give birth earlier. These newborns present with severe weakness, hypotonia, and heart defects. Newborns don’t achieve any motor milestones. Often, these babies have facial diplegia (facial paralysis), a lack of reaction to stimuli, and a congenital heart defect.1,2,3  Patients diagnosed with SMA type 0 die from respiratory failure by 6 months of age and sometimes by within the first month after birth.

Children who have noticeable SMA symptoms at or shortly after birth usually are very weak; have difficulty breathing, sucking, and swallowing; and never reach the developmental milestone of being able to sit on their own (SMA type 1 or Werdnig-Hoffmann disease). With technology such as mechanical ventilation and feeding tubes to assist with breathing and nutrition, children with SMA type 1 can survive for a number of years. For more information about the current state of research and new treatments, see Research or MDA Celebrates FDA Approval of Zolgensma for Treatment of Spinal Muscular Atrophy in Pediatric Patients.

SMA type 2 (aka Dubowitz disease, or intermediate SMA) symptoms begin in babies at approximately 3 to 15 months of age who learn to sit unassisted but do not stand or walk independently. This presentation accounts for around 20% of all cases of SMA. Muscle weakness is predominantly proximal (close to the center of the body) and involves the lower limbs more than the upper limbs. Usually, the face and the eye muscles are unaffected.4 Although respiratory complications are a constant threat, children with SMA type 2 usually live to young adulthood, and many live longer.5

When muscle weakness begins in older children and teens who learn to stand and walk but lose these abilities later in life, the disease may be labeled SMA type 3 (aka mild SMA, juvenile onset, or Kugelberg-Welander disease). SMA type 3 accounts for around 30% of cases of SMA. Although some with type 3 stop walking in adolescence, others walk well into their adult years. Most of the patients develop foot deformities, scoliosis, and respiratory muscle weakness.

SMA that comes on in the late teens or adulthood is called type 4, or late-onset SMA. Life span is generally normal in this type. Patients are able to achieve all motor milestones and maintain their ambulation throughout life.4

In SMA types 1 through 4, the muscles closer to the center of the body (proximal muscles) usually are more affected, or at least affected much sooner, than the muscles farther away from the center. For example, the muscles of the thighs are weaker than the muscles of the lower legs and feet.

Legs tend to weaken before the arms. The hands may weaken eventually, but they usually stay strongest the longest, and, even if they do weaken, they usually remain strong enough for typing on a computer keyboard and other basic functions of modern life.

The most serious danger in SMA comes from the weakness of the muscles necessary for breathing. Careful attention to respiratory function is needed throughout life, with prompt attention to infections. Your doctor can help you with details of maintaining respiratory health, including clearance of secretions and perhaps assisted ventilation (not necessarily around-the-clock).

Another medical complication in SMA is spinal curvature, usually a side-to-side type of curvature called scoliosis. Scoliosis occurs because of weakness of the muscles that normally support the spine, which is a flexible column. Scoliosis can be very uncomfortable, interfere with position and mobility, and damage a child’s (or adult’s) body image. Some studies have shown that spinal curvatures, if they’re severe, can interfere with breathing.

Many children with SMA start to show a scoliotic curve early in life, which often is treated with a brace until the right time for surgery is reached. Surgeons generally like to wait until growth is complete or nearly so before surgically straightening and fusing the spine. They also take into account a child’s pulmonary function and how fast the spinal curve is likely to progress

Causes

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 40–60Trusted Source 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 4Trusted Source chance that the child will inherit it.

Spinal Muscular Atrophy Diagnosis

SMA can be hard to diagnose because the symptoms may be similar to other conditions. To help figure out what's going on, your doctor may ask you:

• Has your baby missed any developmental milestones, such as holding their head up or rolling over?
• Does your child have trouble sitting or standing on their own?
• Have you seen your child have trouble breathing?
• When did you first notice the symptoms?
• Has anyone in your family had similar symptoms?

Your doctor may also order some tests that can help make a diagnosis. For example, they may take a blood sample from your child to check for missing or broken genes that can cause SMA. Your doctor could also order a blood test that checks for creatine kinase (CK). It’s an enzyme that leaks out of weakening muscles. High blood CK levels aren’t always harmful but do show possible muscle damage.

Other tests rule out conditions that have similar symptoms:

Nerve tests, such as an electromyogram (EMG). Your doctor puts small patches on your child's skin and sends electrical impulses through the nerves to see if they are sending messages to the muscles.

CT. This is a powerful X-ray that makes detailed pictures of the inside of your child's body.

MRI. This uses powerful magnets and radio waves to make pictures of organs and structures inside your child.

Muscle tissue biopsy. In this test, the doctor removes muscle cells through a needle in the muscle or through a small cut in your child's skin.

Questions for Your Doctor

• Have you treated others with this condition?
• What treatments do you recommend?
• Is there therapy that can help keep my child's muscles strong?
• What can I do to help my child become more independent?
• How can I get in touch with others who have family members with SMA?
• Spinal Muscular Atrophy Treatment

The FDA has approved three medications to treat SMA: nusinersen (Spinraza), onasemnogene abeparvovec-xioi (Zolgensma) and risdiplam (Evrysdi). Both are forms of gene therapy that affect the genes involved in SMA. The SMN1 and SMN2 genes give your body instructions for making a protein that helps with controlling muscle movement.

Nusinersen (Spinraza). This treatment adjusts the SMN2 gene and lets it make more protein. It's used for both children and adults with SMA. Your child's medical team will inject the drug into the fluid around their spinal cord. Including preparation and recovery time, this can take at least 2 hours and will need to be done several times, followed by another dose every 4 months. Studies show it helps about 40% of people who use it by making them stronger and slowing the disease.

Onasemnogene abeparvovec-xioi (Zolgensma). This involves replacing the problem SMN1 gene. It's used for children under 2 years old. Your child's medical team will put a tiny tube called a catheter directly into a vein in their arm or hand (an IV). Then, they'll send a copy of the SMN gene through the tube into a specific group of motor neuron cells. This will need to be done only one time. In studies, onasemnogene abeparvovec-xioi helped children with SMA reach certain developmental milestones faster, like controlling their heads or sitting without support.

Risdiplam (Evrysdi). This treatment works to stop the SMN2 genes from disrupting the protein production,  allowing the protein to reach the nerve cells as needed. Your child takes it orally once a day after a meal. The dosage is determined by their weight.Clinical trials showed improved muscle function after 12 months in 41% of those taking it.

Besides gene therapy, your doctor may suggest a few other ways to help manage symptoms:

Breathing. With SMA, especially types 1 and 2, weak muscles keep air from moving easily in and out of the lungs. If this happens to your child, they may need a special mask or mouthpiece. For severe problems, your child may use a machine that helps them breathe.

Swallowing and nutrition. When muscles in the mouth and throat are weak, babies and children with SMA can have a hard time sucking and swallowing. In that situation, your child may not get good nutrition and may have trouble growing. Your doctor may suggest working with a nutritionist. Some babies may need a feeding tube.

Movement. Physical and occupational therapy, which use exercises and regular daily activities, can help protect your child's joints and keep muscles strong. A therapist may suggest leg braces, a walker, or an electric wheelchair. Special tools can control computers and phones and help with writing and drawing.

Back issues. When SMA starts in childhood, children can get a curve in their spine. A doctor may suggest that your child wear a back brace while their spine is still growing. When they’ve stopped growing, they may have surgery to fix the problem.

 Caring for Your Child With Spinal Muscular Atrophy

There's a lot you can do as a family to help your child with some of the basic tasks of daily life. A team of doctors, therapists, and support groups can help you with your child's care and let them keep up with friendships and activities with your family.

Your child will probably need lifelong care from different types of doctors. They may need to see:

• Pulmonologists, doctors who treat lungs
• Neurologists, specialists in nerve problems
• Orthopedists, doctors who treat bone problems
• Gastroenterologists, specialists in stomach disorders
• Nutritionists, experts in the way food affects your child's health
• Physical therapists, people trained in using exercise to improve your child's motion

This team can help you make decisions about your child's health. It's important not to let yourself get overwhelmed by the task of managing care. Check for support groups that can let you share your experiences with others who are in similar situations.

Spinal Muscular Atrophy Outlook

The outlook depends on when symptoms started and how severe they are. If your child has type 1, a severe form of SMA, they may start having symptoms anywhere from birth to age 6 months. In general, most babies with this type start showing signs of the disease by age 3 months. You'll start to notice that their development is delayed, and they may not be able to sit up or crawl.

Even though children with this type usually don't live beyond age 2, with help from your doctors and support team, you can make their life comfortable.

In other types of SMA, doctors can help ease a child’s symptoms for many years and, in many cases, throughout their life.

Keep in mind that every child or adult who has SMA will have a different experience. A treatment plan that's made just for your child can help them have a better quality of life.

Spinal Muscular Atrophy Support

Organizations like these can offer you support:

Cure SMA. It funds research aimed at treating and curing SMA. Its SMArt Moves initiative focuses on the importance of early diagnosis and treatment. Cure SMA also offers support for people and families through local chapters and its website, including offering information to those newly diagnosed.

Muscular Dystrophy Association. This group has information and links to services and support groups in your area.

SMA Foundation. Its mission is to boost the search for SMA treatment, working with researchers, developing clinical trials, and helping to educate others about this genetic condition.