Spinal Muscular Atrophy: Causes, Symptoms & Treatments

What is Spinal Muscular Atrophy (SMA)?

Spinal muscular atrophy (SMA) is a genetic disease. It is classified as a motor neuron disease because it affects the lower motor neurons, which are specialized nerve cells in the spinal cord. These motor neurons control muscle movement that is performed voluntarily, such as walking, speaking, swallowing, and breathing. 

In healthy people, the upper motor neurons in the brain send messages to the lower motor neurons, which then connect to muscles to activate them and cause them to contract. 

In people with spinal muscular dystrophy, these signals are disrupted. As a result, the muscles begin to shrink in size and become weak due to inactivity (this is called muscle wasting or muscle atrophy). The muscles most affected by progressive muscle weakness are the proximal muscles (located close to the center of the body), including the shoulders, upper back, hips, and thighs.

SMA is a progressive disease that worsens over time. It causes slow muscle weakness and problems with voluntary muscle movement. The disorder is called spinal muscular atrophy because most of the affected motor neurons are in the spinal cord, and the condition causes muscle atrophy (wasting).

Prevalence of Spinal Muscular Atrophy (SMA)

About 1 in 6,000 babies are born with spinal muscular atrophy. It is one of the most common genetic disorders of childhood and a major cause of death in infancy. SMA can affect children of all ages, but diagnosis in infancy and early childhood is associated with worse outcomes. 

Types of Spinal Muscular Atrophy

Spinal muscle atrophy is classified according to the age at onset into SMA types 0 through 4. 

• SMA type 0 (Prenatal) is the most severe and rarest form of SMA diagnosed in the womb with symptoms discovered before birth. Babies diagnosed prior to birth may not survive past 6 months and are likely to experience severe weakness, as well as trouble breathing and feeding.

• SMA type 1 (Werdnig-Hoffman disease or infantile-onset SMA) is the most common form of SMA and is also severe. It is associated with severe weakness in voluntary muscle movement. SMA type 1 is diagnosed in infants less than 6 months of age. The majority of children with SMA type 1 die before age 2, but newer therapies are improving the prognosis for these babies.

• SMA type 2 (Dubowitz disease or intermediate SMA) develops when the affected child is between 6 and 18 months of age. Babies with SMA type 2 are able to sit up but cannot stand or walk. They may develop respiratory muscle weakness as the disease progresses.

• SMA type 3 (Kugelberg Welander disease or juvenile SMA) is diagnosed when symptom onset occurs between the age 18 months and the teenage years. The maximum motor function achieved in most children with SMA type 3 is the ability to walk and stand for short periods of time, especially in the early course of the disease, although these abilities may be lost with disease progression.

• SMA type 4 (adult SMA) develops during adulthood. The muscle weakness is usually not severe enough to impact a person’s lifespan.

• SMA not linked to chromosome 5 (including Kennedy’s disease) is different from the other SMA types 1 through 4. It is not linked to a survival motor neuron 1 (SMN1) gene mutation and SMN protein deficiency. These forms vary in severity and may involve more distal muscles (muscles located away from the center of the body). 

Causes of Spinal Muscular Atrophy

Genetic Factors

Spinal muscular atrophy types 0 through 4 are caused by mutations (changes in the DNA sequence or genetic flaws) in a gene called the survival motor neuron 1 (SMN1 gene) that is located on chromosome 5. This gene is responsible for making the SMN protein. In people with a mutated gene, there is not enough SMN protein. This lack of SMN protein leads to problems with voluntary skeletal muscles receiving nerve signals.

Having multiple copies of the SMN2 gene is usually associated with less severe symptoms of the condition and the development of the disorder later in life. 

Risk Factors

• Family history: Spinal muscular atrophy (SMA) is an inherited disorder that runs in families. Having a family member with SMA is, therefore, a risk factor for the disorder. 

• Race: SMA is more common in Caucasians compared to other races.

Symptoms of Spinal Muscular Atrophy

The primary symptom of spinal muscular atrophy (SMA) is progressive muscle weakness that gets worse over time. The severity of muscle weakness depends on the type of spinal muscular atrophy and the amount of SMN protein present in the motor neurons. The more SMN protein present, the milder the illness.

Therefore, depending on the type of SMA, symptoms can range from mild to disabling. As mentioned, the earlier in life the disorder develops, the more severe the symptoms and the worse the outlook. 

Spinal muscular atrophy (SMA) affects voluntary skeletal muscles such as those of the shoulders, upper back, hips, and thighs that are close to the center of the body. Motor function in the lower limbs is affected more than the upper limbs. SMA does not affect involuntary muscles, such as those present in the heart or digestive tract. People with SMA have normal sensory function as well as emotional and cognitive development.

SMA type 0 Symptoms

• Severe neonatal hypotonia, also known as “floppy baby syndrome,” is when muscles appear relaxed because of decreased muscle tone.

• Severe weakness.

• Respiratory failure at birth.

• Difficulty feeding.

• Decreased fetal movements in late pregnancy.

• Areflexia (absence of reflexes).

• Stiff and deformed joints.

• Congenital heart defects.

• Death usually occurs in the first 6 months of life.

SMA type 1 Symptoms

• Premature birth.

• Severe muscle weakness.

• Facial paralysis.

• Difficulty breathing, swallowing, and sucking.

• Respiratory muscle weakness.

• Failure to achieve motor milestones.

• Lack of reaction to stimuli.

• Death usually occurs before the age of 2. 

SMA type 2 Symptoms

• May sit unassisted but unable to stand or walk without assistance.

• The face and eyes are usually not affected.

SMA type 3 Symptoms

• Children with SMA type 3 learn to stand and walk but may lose these abilities later in life during the adolescent or adult years.

• Scoliosis (a curve in the spine) can develop due to weakness of the back muscles.

• Foot deformities.

• Respiratory muscle weakness.

SMA type 4 Symptoms

• People with later-onset SMA type 4 typically have mild muscle weakness. They are able to achieve all motor milestones and remain ambulatory throughout life.

Progressive Symptoms

The most serious complication of spinal muscular atrophy is progressive respiratory muscle weakness. Severe scoliosis (curvature of the spine) with disease progression can also affect breathing. 

How Do Doctors Diagnose SMA?

Clinical Examination and Tests:

Healthcare providers may order the following tests to find out the cause of muscle weakness and atrophy (wasting):

• Electromyography (EMG), a test that shows how muscles receive signals from nerves.

• Muscle biopsy, a test that involves looking at a sample of muscle tissue under the microscope. Find out “What to Expect When Doctors Take a Biopsy.”

Genetic Testing

A simple blood test can identify about 95% of all SMA cases by checking for deletion or mutation of both SMN1 genes (one from each parent).

Learn about Genetic Testing During Pregnancy: How Does It Work?

Newborn Screening

Newborn babies in the US are screened for many diseases, including spinal muscular atrophy (SMA). This can be done with a simple blood test shortly after birth. This blood test is done in all babies, including those who have no symptoms and appear healthy, to identify different health conditions. 

If newborn screening shows that a baby may have pre-symptomatic SMA, the doctor will order more tests to confirm the diagnosis. This is important because early diagnosis of spinal muscular atrophy can ensure early treatment and prevent serious complications.

Differential Diagnosis

Disorders that can cause symptoms similar to spinal muscular atrophy (SMA) include other genetic conditions and neuromuscular disorders such as X-linked infantile SMA, Prader-Willi syndrome, congenital muscular dystrophy, Duchenne muscular dystrophy, amyotrophic lateral sclerosis (ALS), and others. Some of the non-inherited conditions that may mimic the signs and symptoms of SMA include botulism and Guillain-Barre syndrome.

What Precautions Should Be Taken For Spinal Muscular Atrophy?

Spinal muscular atrophy is a genetic condition with autosomal recessive inheritance. It cannot be prevented, and there is no way to cure SMA. It occurs due to a random genetic change that's unpredictable. SMA is not the result of something the biological parents did before or during the pregnancy. 

However, it is possible to identify carriers of the faulty gene (people who have one faulty copy and one functioning copy of the SMN1 gene). Carriers do not develop symptoms of SMA, but they can pass on the faulty gene to their children. Many times, carriers do not know they have a faulty SMN1 gene until their child is diagnosed with SMA. A simple blood test (DNA test) can identify SMA carriers. 

Women who are planning a pregnancy or are pregnant already can undergo carrier screening for SMA and other genetic disorders. If a woman is found to be a carrier, her partner can be tested. If both parents are carriers of SMA, there is a 25% chance the child will be unaffected, a 50% chance the child will be a carrier, and a 25% chance the child will have SMA.

Treatment Options for Spinal Muscular Atrophy

Medical Treatments

Medications for SMA may help muscle function, maintain motor neurons, and lengthen life. However, medications may not cure SMA and are not always suitable for children and adults who have been diagnosed with SMA. Whether medicines (gene therapy) can be prescribed depends on several factors, including the type of SMA, the patient’s age, and symptoms. Gene replacement therapy (disease-modifying therapy) that may be used to treat certain types of SMA includes:

• Risdiplam (Evrysdi) helps to produce SMN protein throughout the body. It is given as a liquid once daily after a meal.

• Nusinersen (Spinraza) works with the SMN2 gene to increase SMN protein production. It is given as an injection into the spine. The first three loading doses are administered at 14-day intervals; the fourth loading dose is given 30 days after the third dose. A maintenance dose is administered once every four months. 

• Onasemnogene abeparvovec-xioi (Zolgensma) is a gene therapy that replaces the nonworking SMN1 gene with a healthy copy of the SMN gene. It is given as a one-time injection. 

Assistive Devices

Braces, walkers, wheelchairs, and other assistive devices can help people with SMA maintain their independence for as long as possible.

Physical Therapy and Rehabilitation

Physical and occupational therapy helps to keep the joints flexible and prevent joint contractures. These therapies can also help to slow the progression of muscle weakness and muscle wasting. Speech therapy can help with speech, chewing, and swallowing to maintain nutrition and prevent aspiration (inhaling food or fluids into the airways and lungs) in children with severe SMA.

Scoliosis Treatment

Scoliosis (a curve in the spine) can develop in people with SMA due to weakness and wasting of the back muscles. This can be uncomfortable and may affect mobility and breathing. Scoliosis is treated with pain medications, braces, or surgery, depending on the severity of the spinal curvature and the risk of it worsening over time. 

Supportive Care

Progressive respiratory muscle weakness over time in people with SMA can affect respiratory function (movement of air in and out of the lungs). This puts them at risk of developing serious respiratory infections. Chest muscle weakness increases the risk of restrictive lung disease. Therefore, a child or adult with SMA may need monitoring with a pulse oximeter to check oxygen saturation in the blood. They may also need some form of breathing support. Respiratory failure due to respiratory muscle weakness is the usual cause of death in children with SMA types 0,1 and 2.

Dietary Modifications

Nutrition is especially important for children with SMA due to problems with chewing and swallowing. The child’s healthcare team will recommend feeding through a gastrostomy tube if necessary.

Children with SMA who live beyond early childhood can develop obesity due to reduced physical activity compared to healthy children. Eating a healthy diet and avoiding empty calories is particularly important for these kids. 

What is Life Like for a Person with SMA?

Can a Baby Live with SMA?

Whether a baby can live with SMA depends on the type of SMA. Babies with type 0 SMA do not usually live beyond 6 months of age. Babies with type 1 SMA usually don’t live past 2 years old, although with advancements in medical treatment, they are starting to live longer. Babies with type 2 SMA can live to young adulthood or longer. Children with type 3 SMA have an almost normal life expectancy. SMA type 4 (adult-onset) does not usually affect life expectancy.

Daily Activities

Children with SMA may have trouble standing, walking, running, jumping, and climbing stairs. They often need assistive devices to stand and walk due to muscle weakness in the legs. Later in life, these children may lose the ability to stand or walk independently, needing a walker or wheelchair to get around. 

Occupational therapy can help a child with SMA learn exercises to carry out daily activities independently, such as bathing and getting dressed. Physical therapy can teach a child with SMA breathing exercises to strengthen the respiratory muscles as well as other muscles.

Life at School 

Children with SMA have normal emotional and intellectual development and often have above-average intelligence. However, they may need help with writing, using a computer, and extra-curricular activities such as painting due to hand muscle weakness.

Sports and Physical Activities

Children with SMA type 3 can participate in most physical activities but may get tired sooner than other kids due to muscle weakness. Kids who are in wheelchairs may be able to enjoy wheelchair-adapted sports like tennis or soccer. Swimming in a warm pool is a popular physical activity for kids with types 2 and 3 SMA.

Support Resources and Communities

Here are some resources for families of individuals living with SMA:

• MDA (Muscular Dystrophy Association) has educational material on the disorder.

• Cure SMA's Daily Life Page has information on home life, parenting, equipment, recreation, and more, with separate pages for children and adults with SMA.

• Drugs in Development is the SMA Foundation’s page on new drugs in the pipeline for SMA.

• NCBI's Genetic Test Sites is the National Center for Biotechnology Information’s list of laboratories offering genetic testing for SMA worldwide.

• Available Clinical Trials and Drugs offers a comparative overview of drugs for SMA that are currently approved or in clinical trials.