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Spinal muscular atrophy (SMA) is a rare genetic disorder that causes progressive muscle weakness and atrophy (wasting). It’s caused by a loss of motor neurons, nerve cells in the brain and spinal cord that control movement. SMA occurs in about 1 out of every 11,000 births in the United States. About 1 in 40 to 1 in 60 people in the U.S. is a carrier for the disease, though this rate varies by ethnic and racial background. While SMA impacts a small number of people, it is the leading genetic cause of infant mortality.
Autosomal recessive proximal SMA is the most common form of SMA, accounting for 95 percent of cases. It’s divided into five types: types 0, 1, 2, 3, and 4. These types are categorized based on symptom severity and the age at which symptoms begin. Type 0 is the most severe form of SMA and begins before birth. Type 4 is the mildest and begins in adulthood. Depending on the type of SMA a person has, symptoms can include:
Sometimes, loved ones ask, “What is SMA life expectancy?” or “Can a baby survive SMA?” While there’s no way to know for sure how long anyone will live, life expectancy is often reduced in more severe SMA types. Treatments such as gene therapy and medications that increase survival motor neuron (SMN) protein have made it possible for some people with SMA to reach developmental milestones, have a better quality of life, and live longer.
SMA develops when specific gene mutations (variants, or changes) are inherited from both parents. For SMA types 0 through 4, a person must inherit a mutated survival motor neuron 1 gene (SMN1) from each parent.
The SMN1 gene, located on chromosome 5, is essential for producing survival motor neuron (SMN) protein, which motor neurons need to function. Motor neurons are nerve cells that send signals from the brain and spinal cord to the muscles. In SMA, insufficient SMN protein leads to motor neuron degeneration. As these neurons lose function, they can no longer signal the muscles, causing muscle atrophy. Depending on the severity of SMA, this muscle atrophy can reduce a person’s ability to breathe and move.
The type of SMA a person develops can be influenced by a second gene on chromosome 5 called SMN2. The SMN2 gene produces some survival motor neuron protein, but not enough for normal muscle function. People without SMA usually have one or two copies of SMN2, though they may have more. Among people with SMA, having more copies of the SMN2 gene is associated with a less severe form of the condition.
Other spinal muscular atrophy types, such as distal SMA and SMA with respiratory distress (SMARD), are caused by different gene mutations.
Cases of SMA were first described in the early 1890s by Austrian scientist Guido Werdnig and German scientist Johan Hoffmann, leading to the name Werdnig-Hoffmann disease for what is now known as SMA type 1. The first cases of severe SMA in babies were identified around the same time, in 1899 and 1903. Milder forms of SMA, what might now be considered type 3 or 4, were first described in the 1950s. The classification system used today to describe SMA types 0 through 4 was established in 1991.
Scientific understanding of SMA improved greatly in 1995 when researchers led by French geneticist Judith Melki discovered that 95 percent of all SMA cases are caused by a mutation or deletion in the SMN1 gene. The same research team discovered the SMN2 gene, which is sometimes referred to as the SMA “backup gene,” as it produces limited amounts of the critical SMN protein that supports motor neuron function.
Discovering the role of the SMN genes opened the door for new diagnosis methods and research. Before scientists had identified the SMN1 gene, SMA was diagnosed based on signs and symptoms of disease, rather than genetic testing that can confirm the presence of a genetic mutation.
The SMN gene breakthrough also allowed scientists to begin animal experiments to expand research on the genetic factors that influence SMA. This greater understanding of genetics opened the doors for clinical trials, which were rare before the 1990s.
Clinical trials for SMA have led to improvements in treatment options, including the first SMA treatment approved by the U.S. Food and Drug Administration (FDA) in 2016 – nusinersen (Spinraza). A second treatment for SMA in children under age 2, onasemnogene abeparvovec-xioi (Zolgensma), was approved in 2019. A third, risdiplam (Evrysdi), was approved in 2020. It's the first oral treatment for the condition.
The five main types of SMA comprise 95 percent of SMA cases. All are caused by mutations in the SMN1 gene, and each type is categorized based on the age of onset and severity of symptoms.
Type 0 is among the rarest and most severe forms of SMA. It affects babies before they’re born. Infants with type 0 are born with profound muscle weakness and significant respiratory difficulties, often shortening life expectancy significantly.
Type 1, or Werdnig-Hoffmann disease, represents about 45 percent to 60 percent of all SMA cases, with estimates differing from source to source. Symptoms typically appear before 6 months of age. Babies with type 1 have severe muscle weakness and difficulty breathing, sucking, and swallowing. Without treatment, respiratory problems often lead to a shortened lifespan. Historically, babies with type 1 SMA did not live past 2 years old.
Also known as Dubowitz disease or intermediate SMA, type 2 accounts for about 20 percent to 30 percent of SMA cases. Symptoms generally appear in early childhood, between 6 and 18 months old. Children with type 2 often develop the ability to sit up on their own but rarely develop the ability to stand or walk. With appropriate treatment and therapies, individuals with type 2 can live into young adulthood or beyond.
Type 3 (Kugelberg-Welander disease) develops between 18 months and 30 years old. This less severe form of SMA accounts for 10 percent to 30 percent of cases. The first indications of SMA type 3 may be muscle weakness in the legs that causes falls and or difficulty climbing stairs. Type 3 does not usually cause respiratory problems, but any respiratory involvement can be serious. While people with type 3 experience muscle degeneration, they have a normal life expectancy.
Type 4, also called late-onset SMA, develops in adulthood, usually after age 35. Occurring in less than 1 percent of people diagnosed with SMA, type 4 can cause mild motor impairment. Adults with this type may notice tremors in the hands, a feeling of heaviness in the muscles, numbness, and muscle cramping. People with SMA type 4 have a normal lifespan and tend to remain mobile into older age.
There are several other very rare types of SMA, including SMA with respiratory distress and distal SMA. They affect different muscle groups and have unique symptoms and genetic causes.
Spinal muscular atrophy is usually diagnosed through genetic testing. The genetic test for SMA looks for mutations on the SMN1 gene on chromosome 5. In the past, genetic testing was usually conducted only if a person showed symptoms of SMA or had a family history of the condition. Beginning in 2018, the U.S. Department of Health and Human Services added SMA to the Recommended Uniform Screening Panel, a list of conditions for which newborns are screened within their first 48 hours of life. Today, all 50 states screen newborns for SMA at birth. Cure SMA offers resources for parents and caregivers whose children were diagnosed through routine newborn screening.
Before genetic testing was available, SMA was diagnosed via methods like muscle biopsy and electromyography (EMG). In cases where genetic testing results aren’t conclusive, these methods may still be used. Muscle biopsy involves removing a small sample of muscle tissue for examination for characteristic changes associated with SMA. EMG primarily assesses motor neuron function and detects muscle activity changes that indicate a loss of nerve supply, which is typical of neurogenic conditions like SMA.
Hypotonia (muscle weakness) is the primary symptom of every type of SMA. Muscle weakness can affect motor function and related abilities.
Sucking, chewing, and swallowing problems are most prevalent in babies and children with severe forms of SMA, such as types 0 and 1. These difficulties result from muscle weakness in the mouth and throat, making it hard to eat and drink safely. For some, a feeding tube may be necessary to ensure adequate nutrition.
Motor skill development and mobility is dependent on SMA type. Babies and children with SMA type 0 and type 1 typically never develop the ability to sit up without assistance. Children with type 2 may learn to sit up without support but may lose that ability as the condition progresses.
Occasionally, children with SMA type 2 develop the ability to stand. Those with type 3 SMA, depending on age of onset, may learn to stand and walk independently, though muscle weakness can hinder these abilities over time. Adults with type 4 generally only experience muscle weakness that impacts mobility in their older age.
Weakness in the respiratory muscles can make it difficult for people with SMA to cough effectively, which is essential for clearing mucus and protecting the lungs. This increases the risk of respiratory infections, including pneumonia, and raises the risk of aspiration, where food or liquid enters the airway instead of the esophagus (the tube connecting the mouth to the stomach).
Several additional symptoms can impact function and quality of life for people with SMA. These may include:
Treatment for SMA depends on the type and severity of symptoms. It includes both disease-modifying therapies (DMTs) that address the underlying cause and supportive therapies that help manage symptoms and improve quality of life.
Three FDA-approved DMTs available for SMA: the aforementioned nusinersen, onasemnogene abeparvovec-xioi, and risdiplam. These therapies work by increasing levels of SMN protein in different ways, helping to improve muscle strength and function. While these treatments aren’t cures, studies show they can significantly enhance muscle strength, particularly in infants and young children. Effects in older individuals with SMA are still being studied.
People with SMA may be eligible to participate in clinical trials to receive access to new treatments.
Breathing support can be critical for people with more severe forms of SMA. Noninvasive forms, such as bilevel positive airway pressure (BiPAP), can assist breathing during sleep and be removed when not needed.
For cases where noninvasive support is insufficient, invasive ventilation support may be necessary. Approaches include an endotracheal tube for short-term support or a tracheostomy, a surgically placed breathing tube, for longer-term or permanent assistance.
Given the potential permanence of these interventions, discussions about long-term care and end-of-life preferences are recommended. Respiratory therapy, which can help strengthen weak breathing muscles, is also a valuable component of respiratory support.
Feeding tubes may be necessary in cases where muscle weakness affects a person’s ability to chew or swallow. Depending on individual needs, tubes can be nasogastric (inserted through the nose into the stomach) or surgically placed through the abdomen, either into the stomach (gastrostomy) or small intestine (jejunostomy).
A variety of supportive therapies can improve daily function, quality of life, and mobility for people with SMA:
SMA is a complex condition that affects each person differently. Fortunately, effective treatments are available that may improve quality of life and, in some cases, extend life expectancy. Open communication with your own or your loved one’s health care team is essential in navigating SMA’s unique challenges. By discussing treatment options, supportive therapies, and any changes in symptoms, you can work together to ensure the best possible care and support.
On mySMAteam, the social network for people with spinal muscular atrophy and their loved ones, more than 2,600 members come together to ask questions, give advice, and share their stories with others who understand life with spinal muscular atrophy.
Are you or a loved one diagnosed with SMA? Share your experience in the comments below, or start a conversation by posting on your Activities page.
Joseph V. Campellone, M.D.
is board-certified in neurology, neuromuscular disease, and electrodiagnostic medicine. Review provided by VeriMed Healthcare Network.
Learn more about him here.
Alison Channon
has nearly a decade of experience writing about chronic health conditions, mental health, and women's health.
Learn more about her here.
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I feel I need to talk to my doctor as some of these conditions I have experienced for yers now are worse,thanku fo the insite.
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