Spinal Muscular Atrophy
What is spinal muscular atrophy?
Spinal muscular atrophy (SMA) refers to a group of hereditary diseases which affect motor neurons. Motor neurons are specialized nerve cells in the brain and spinal cord that control movement in the arms, legs, face, chest, throat, and tongue, as well as skeletal muscle activity, including muscles used for speaking, walking, swallowing, and breathing. The skeletal muscle weakness caused by SMA is often more severe in the trunk (chest) and upper leg and arm muscles than in muscles of the hands and feet. People with SMA experience respiratory infections, scoliosis, and joint contractures (chronic shortening of muscles and tendons).
The most common form of SMA is caused by changes in a gene known as the survival motor neuron gene 1 (SMN1). Traditionally, there are five types of this form of SMA, which are classified based on the average age of onset and severity of symptoms. The traditional classification of SMA caused by problems with the SMN1 gene include:
- Type 0 is a very rare and severe type of SMA with symptoms beginning prior to birth. At birth, the infant has severe weakness and difficulty breathing and feeding.
- Type l (also known as Werdnig-Hoffman disease or infantile-onset SMA) is the most common form of SMA. It is usually evident before 6 months of age. Symptoms include severe muscle weakness and trouble breathing, coughing, and swallowing.
- Type ll is usually first noticed between 6 and 18 months of age. Children with this type of SMA can sit without support but are unable to stand or walk without help.
- Type lll (also known as Kugelberg-Welander disease) shows symptoms after 18 months of age. Children can walk independently but may have difficulty doing so. They may also have trouble running, rising from a chair, or climbing stairs.
- Type IV develops after 18 years of age. Symptoms include mild to moderate leg muscle weakness and other symptoms.
There is a gene very similar to SMN1 called SMN2, which may be present in multiple copies. Although the SMN2 gene makes much less of the SMN protein than the healthy SMN1 gene, extra copies of the SMN2 gene are associated with the less severe forms of SMA (Types II-IV).
With the development of new treatments for SMA, the expected course of disease is improving, especially for people with SMA Types I and II. As we learn more about SMA and develop new treatments, diagnosis and classification of SMA is involving to include both clinical symptoms and genetic information.
Who is more likely to get spinal muscular atrophy?
Most cases of SMA occur when the affected gene is passed down from the person’s parents. It is an autosomal recessive disorder, meaning that the affected individual has two mutated genes, typically inheriting one faulty gene from each parent. Those with only one mutated gene are carriers of the disease but will not have any symptoms. SMA can arise sporadically in an affected individual (without inheriting two mutated genes), but this is extremely rare.
Individuals who have a family member with SMA or a family member who is a carrier may be at risk of being a carrier themselves. Genetic carrier testing is available to detect mutations in the SMN1 gene and identify possible carriers.
People living with SMA have insufficient levels of the survival motor neuron (SMN) protein, which maintains the health and normal function of motor neurons. Insufficient levels of SMN protein leads to loss of motor neurons in the spinal cord and causes weakness and wasting of the skeletal muscles. The most common form of SMA is caused by the SMN1 gene; however, there are other forms of SMA associated with other genes.
Less common SMA forms are caused by changes in other genes, including the:
- IGHMBP2 gene on chromosome 11
- MORC2 gene on chromosome 22
- UBA1 gene on the X chromosome
- DYNC1H1 gene on chromosome 14
- BICD2 gene on chromosome 9
- TRPV4 on chromosome 12
How is spinal muscular atrophy diagnosed and treated?
Diagnosing SMA
To diagnose SMA, a doctor will obtain a thorough medical history and perform a physical exam. Then, they will conduct a neurological exam to understand the person’s motor function.
A blood test is available to look for mutations or deletions of the SMN1 gene. This test identifies at least 95% of SMA Types I, II, and III, and may reveal if a person is a carrier for SMA. If the SMN1 gene is normal or the individual's history and examination are not typical of SMA, other diagnostic tests include:
- Electromyography to record the electrical activity of the muscles during contraction and at rest
- Nerve conduction velocity studies to measure the nerve's ability to send an electrical signal
- Muscle biopsy may be used to diagnose other conditions with symptoms similar to SMA
Treating SMA
Several treatments have been developed for SMA that preserve motor neurons, improve muscle function, and extend lives, but these are not cures. Treatment early in life tends to provide more benefit than treatment later in life, as older people who have been living with SMA and have experienced greater loss of motor neurons.
FDA-approved treatments for SMA include:
- Nusinersen (Spinraza™) increases production of the SMN protein and is approved to treat children and adults with SMA. This medication is administered via lumbar puncture.
- Onasemnogene abeparovec-xioi (Zolgensma™) is a gene therapy for children less than two years old who have infantile-onset SMA (Type I). This therapy replaces the SMN1 gene function by delivering a new working SMN gene to the person’s motor neurons. This treatment has been shown to improve muscle movement, function, and survival.
- Risdiplam (Evrysdi™) is an orally administered drug to treat people age two months and older. Risdiplam works by increasing the concentration of SMN protein in the body.
People with SMA can benefit from physical therapy, occupational therapy, and rehabilitation to help improve posture, prevent joint immobility, and slow muscle weakness and atrophy. Stretching and strengthening exercises may help reduce joint contractures, increase range of motion, and improve circulation. Some individuals may require additional therapy for speech and swallowing difficulties. Assistive devices such as supports or braces, orthotics, speech synthesizers, and wheelchairs may be helpful to improve functional independence.
It is important the people with SMA get proper nutrition to help them maintain weight and promote muscle function. People who cannot chew or swallow may require a feeding tube. Non-invasive ventilation can improve breathing during sleep, and some individuals also may require assisted ventilation during the day due to muscle weakness of the respiratory muscles (along the chest).
What are the latest updates on spinal muscular atrophy?
NINDS, a component of the National Institutes of Health (NIH), conducts and supports research on SMA aimed at finding new and better treatments, identifying genetic mutations and other factors that may influence the development of these diseases, and developing biomarkers (biological measures of a disease) and outcome measures that can be used in research studies.
NINDS-supported scientists are:
- Studying cell function in SMA in an effort to identify critical cellular processes that could be targeted to improve outcomes for people with SMA.
- Using gene editing tools to develop strategies to correct SMN gene mutations, with the goal of developing and improving treatments for SMA and other genetic motor neuron diseases.
- Studying the function of SMN protein to learn how reduced SMN protein causes SMA.
- Building on recent advances to discover new therapeutic approaches that may be suitable for use in combination with current SMN-inducing treatments.
In a broader effort, NINDS scientists are studying inherited neurological disorders, including SMA, to learn about their natural history and the role heredity plays in their development. Other NINDS scientists are using ultrasound and a new technique, called electrical impedance myography, to observe nerves and muscles, learn more about how they function, and evaluate the disorders that affect them.
More information about SMA research supported by NINDS and other NIH Institutes and Centers can be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects.
How can I or my loved one help improve care for people with spinal muscular atrophy?
Consider participating in a clinical trial so clinicians and scientists can learn more about SMA. Clinical research with human study participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.
All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with SMA at Clinicaltrals.gov, a searchable database of current and past federal and private clinical studies.
Where can I find more information about spinal muscular atrophy?
Information may be available from the following organizations and resources: