Spinal muscular atrophy (SMA) is a rare disease involving nerve cells called motor neurons, which normally help the body move muscles. SMA affects 1 in every 6,000 to 10,000 children. Below is information about SMA and its SMA subtypes, including how they differ from one another in terms of signs, symptoms, and outcomes for affected children.

Genetics

• SMA is a condition with a clear genetic cause.
• About 10,000 to 25,000 children and adults in the U.S. currently live with SMA.
• 1 in every 50 people are carriers of a mutated copy of the gene that is linked to SMA, called the survival motor neuron 1 (SMN1) gene.
• SMA is an autosomal recessive condition, which means you need two mutated copies of a certain gene (one mutated copy from each parent) to have the condition.
• The SMN genes that produce SMN protein — responsible for the health of motor neurons — are located on the fifth chromosome.
• SMN1 is the main gene that produces SMN protein, and mutations in SMN1 are largely what drive SMA.
• SMN1 is the primary gene whereas SMN2 is a backup gene that people can have various copies of.
• The more copies of the SMN2 gene a person has, the more SMN protein is available, which can help compensate for an SMN1 mutation and lead to milder SMA.

Types of SMA

• There are four types of SMA.
• SMA type 1 is the most severe form of SMA, SMA type 4 is the least severe, and type 2 and type 3 are in the middle (sometimes referred to as intermediate SMA).
• SMA type 1 is the most common type, making up about 60 percent of all cases of SMA.
• SMA type 1 may be called infantile SMA or Werdnig-Hoffmann disease.
• SMA type 3 is also called Kugelberg-Welander disease.
• SMA type 3 begins later in childhood (after 18 months in most cases) once the child has already begun to walk and run independently.
• SMA type 4 is also called adult-onset SMA, because its symptoms usually start in people after the age of 30.

Signs and Symptoms of SMA

• SMA is a motor neuron disease, meaning that it slowly destroys the nerves that go from the spinal cord to control the muscles throughout the body, including the arms, legs, and the muscles used for breathing (respiratory muscles) and swallowing.
• The form of SMA a person has determines which muscles are affected, age of onset, and how fast the symptoms appear.
• Muscle weakness can lead to hypotonia, or decreased muscle tone, from lack of control and use.
• People with SMA who survive into childhood and adulthood often eventually develop an abnormal curvature of the back, known as scoliosis, due to loss of postural muscles located in the back.
• SMA type 1 affects not only the arms and legs, but also infants’ ability to swallow, suck, and eventually breathe and clear their airways.
• Infants with SMA type 1 become prone to lung infections (such as pneumonia) and collapsed lungs during their early months.
• SMA type 2 usually starts in infancy and mostly affects the arm and leg muscles closer to the trunk (proximal muscles). It usually has lesser effects on the lungs and swallowing compared to type 1.
• Children with SMA type 2 usually can sit but lose their ability to walk.
• People with SMA type 3 (juvenile-onset SMA) will gradually need more help with walking and standing in their teenage or young adult years, but not as infants or young children.
• Most people with SMA type 4 remain mobile and live full, mostly unrestricted lives.

Diagnosis

• Doctors usually confirm an SMA diagnosis using genetic testing to look for mutations in SMN1 and SMN2 genes.
• Muscle biopsy and electromyography are often performed to look more closely at muscles to see if weakness may be due to other causes, such as muscular dystrophy, another muscular disease.

Treatment

• Supportive care services, such as physical therapy and occupational therapy, can teach people living with SMA exercises and tools to help maintain independence.
• The main drug for SMA approved by the U.S. Food and Drug Administration is Spinraza (nusinersen). The medication works by binding to part of the SMN2 gene so that more normal copies of the SMN protein are produced to help maintain muscle strength.
• Nusinersin is delivered via injection into the space around the spinal cord.
• The gene therapy drug Zolgensma (onasemnogene abeparvovec-xioi) is approved for use in children younger than 2.
• Onasemnogene abeparvovec-xioi uses a virus to deliver and insert a functional copy of the SMN1 gene into the body’s DNA.
• Multiple other possible gene therapies are currently being studied in clinical trials.

Outcome

• The expected lifespan for a child born with SMA type 1 is short, with the majority of children passing away before their second birthday.
• People with SMA type 2 typically live into adulthood.
• Most people living with SMA types 3 and 4 usually go on to have near-normal to normal life expectancy and quality of life.

Talk With Others Who Understand

On mySMAteam — the social network for people with children with SMA and their loved ones — members come together to ask questions, give advice, and share their stories with others who understand life with spinal muscular atrophy.

Do you have something to add to the conversation? Share your experience in the comments below, or start a conversation by posting on mySMAteam.