Genetic Diseases

Spinal Muscular Atrophy (SMA)

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Published on October 7, 2024
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Spinal muscular atrophy (SMA) is a rare genetic disorder that causes severe muscle weakness. SMA usually affects children, and is typically diagnosed in the first 18 months of life.

In its most serious forms, SMA can prevent babies from ever crawling or sitting up, and leads to death at a very young age. For others, SMA may create lifelong mobility challenges, but does not otherwise affect lifespan or intellectual development.

Overview

What Is Spinal Muscular Atrophy (SMA)?

SMA is a genetic neuromuscular disorder marked by the loss of nerve cells that control voluntary muscle movement. People with SMA have weakened muscles, especially in the legs and core. For some children, this muscle atrophy will lead to life-threatening breathing problems; for others, it creates mobility challenges. SMA does not affect sensory ability, emotional development or intelligence.

Most types of SMA are caused by mutations in a gene known as SMN1 (survival motor neuron 1) that’s located on chromosome 5. This mutation causes the death or dysfunction of the nerves that control voluntary muscle movement. Symptoms can appear before birth or as late as adulthood. The earlier SMA symptoms appear, the more severe it is.

Illustrative graphic titled How Spinal Muscular Atrophy (SMA) Affects the Body shows hip/ thighs weakness, difficulty breathing, lack of muscle tone, diminished reflexes, scoliosis, difficulty swallowing, back/shoulder weakness. Everyday Health logo
SMA causes muscle weakening that can lead to significant disabilities.
Everyday Health

Types of SMA

Most cases of SMA are classified by age of onset and severity of symptoms.

  • Type 0 is characterized by reduced fetal movement during pregnancy. At birth, babies display severe weakness and often don’t react to stimuli. Babies with type 0 SMA may live fewer than six months.
  • Type 1 (also known as Werdnig-Hoffman disease) is the most common type of SMA, with onset typically occurring between birth and 6 months of age. Babies with type 1 SMA typically don’t learn to sit independently, and may not live beyond age 2 years.
  • Type 2 (also called intermediate SMA or Dubowitz disease) is usually first noticed between 6 and 18 months of age. Children may sit independently but cannot stand or walk without help. Traditionally, these children can live until their twenties or thirties before respiratory issues are likely to cause an early death.
  • Type 3 (also known as Kugelberg-Welander disease) produces symptoms after 18 months of age. Children are usually able to stand and walk, although often with difficulty. Life expectancy is unaffected.
  • Type 4 causes symptoms at age 18 or later, usually in the twenties or thirties. Symptoms include mild to moderate leg muscle weakness, although people are mostly able to maintain mobility throughout life and are not otherwise affected by the condition.

There are a number of other especially rare forms of SMA not covered in this article that are caused by mutations in different genes and vary greatly.

Signs and Symptoms of SMA

In rare cases, the symptoms of SMA can be identified before birth because of reduced fetal movement. More commonly, the condition becomes evident during a child’s first 18 months:

  • Muscle weakness and lack of muscle tone, especially in the thighs, hips, shoulders, and back
  • Reduced mobility
  • Inability to reach early developmental milestones, such as sitting up or crawling
  • Spinal curvature (scoliosis)
  • Diminished reflexes and motor skills
  • Difficulty swallowing
  • Difficulty breathing

The severity of these symptoms differs significantly based on the age that SMA develops:

  • The youngest babies with SMA may never be able to sit up or crawl, and will experience critical breathing and swallowing problems by the age of 2.
  • Children who are diagnosed between the ages of 6 and 18 months generally have a slower onset of symptoms. They will probably require a wheelchair, but can enjoy a good quality of life before their condition progresses to a dangerous state.
  • Adolescents and adults who are diagnosed with SMA lose muscle strength much more slowly and may never suffer from difficulty breathing or swallowing.

The Genetics of Spinal Muscular Atrophy (SMA)

SMA is a genetic condition: People inherit the disease from their biological parents. It is a recessive disorder, which means that SMA development requires two nonworking gene variants, one from each parent.

People with only one nonworking gene variant are considered SMA carriers and don’t develop the disease themselves, although they may pass it on to their children if the other parent is also a carrier. About 2 percent of American adults are carriers of SMA. If both parents are carriers, there’s a 1 in 4 chance that their child will develop SMA.

How Is SMA Diagnosed?

Muscle weakness and loss of motor skills are often the first symptoms to raise suspicion of the disorder. Doctors may conduct an in-office physical examination and check for secondary symptoms, such as lack of muscle reflexes, to help to distinguish SMA from other conditions with similar symptoms, such as muscular dystrophy.

The easiest and most accurate way to diagnose SMA is with a genetic test, which usually only requires a blood or saliva sample. Other tests examine muscle fibers or measure nerve conductivity within the muscles.

Some cases of SMA are diagnosed before birth. With a blood test, you can learn if you are a carrier of the nonworking gene that causes SMA. The American College of Obstetricians and Gynecologists recommends that all women who are pregnant or planning to become pregnant undergo screening for a variety of genetic disorders, including SMA. If the mother is found to be an SMA carrier, the father should also be tested.

If blood tests show that both parents are known carriers, it’s then possible to test the growing fetus in the womb. Doctors can sample either the placenta or the amniotic fluid to determine whether the fetus has inherited two copies of the SMA gene variant.

Early identification of SMA provides an opportunity for early access to treatment, even before symptoms develop, which research shows can improve outcomes.

Can SMA Be Prevented?

SMA cannot be prevented.

If both parents learn through genetic testing they are SMA carriers, they have options to reduce the chance that they will give birth to a child who will develop SMA. Parents can prevent their child from having SMA by using in vitro fertilization (IVF), which allows a clinic to screen embryos for the disorder before implantation.

If both parents are carriers of the SMA gene variant, they have a 25 percent chance of having a child with SMA, a risk that remains the same for each pregnancy.

Treatment and Medication Options for SMA

There is no cure for SMA, but treatment and medication can improve the quality of life and outlook for people of all ages with the condition.

Medication Options

There are a three drugs approved to treat SMA, all of which have only been approved within the last decade:

  • nusinersen (Spinraza), approved in 2016, was the first drug approved specifically for SMA.

     Nusinersen is an injection administered into the spinal column; it can greatly increase mobility and physical function.

  • onasemnogene abeparvovec (Zolgensma) is a newer gene therapy for children under two years of age diagnosed with SMA, including those who are presymptomatic. This is a one-time intravenous infusion that delivers a copy of the healthy SMN gene to affected muscles, resulting in improved mobility and strength.

  • risdiplam (Evrysdi) is an oral medication for adults and children of any age with SMA which can increase the body’s natural production of healthy SMN genes.

Though these three medications have wonderful potential for the treatment of SMA, they can be extraordinarily expensive. Zolgensma, in particular, has been called “the world’s most expensive drug.”

 In the United States, Medicaid and most private insurers cover Zolgensma for children, but they may have especially strict criteria for who qualifies.

Clinicians may also choose to prescribe other drugs that do not address the root cause of SMA but can help improve health and quality of life, such as muscle relaxants to reduce muscle stiffness.

Physical Therapy

Children with SMA may have difficulty performing daily tasks.

  • Occupational therapy can help improve daily living as well as time at school and work by teaching people with SMA how to improve their ability to perform chores, prevent complications, and conserve energy.
  • Physical therapy can help improve posture, keep joints flexible, and generally slow the progression of muscle atrophy.
  • Speech-language pathologists can help with speech problems and swallowing difficulties common among those with SMA. Proper feeding is essential both to avoid aspiration (inhaling food or fluid into the lungs) and ensure good nutrition.

Assistive Devices

A variety of assistive devices can improve quality of life for those with SMA.

  • Standers, walkers and different kinds of powered and manual wheeled vehicles can help even very young children explore the world despite having weak muscles.
  • Braces for the back can slow development of abnormal spinal curvature.
  • A gastrostomy tube helps patients who are not able to swallow food safely by allowing liquid nutrition to enter the stomach directly, bypassing the mouth, throat, and esophagus.

  • A BiPAP (bilevel positive airway pressure) machine delivers fresh air to the lungs, and helps remove air as you exhale.

  • Vibrating vests can be used several times a day to help to loosen mucus in the throat and improve airflow.

  • Cough machines and nebulizers can help children who cannot cough effectively to clear their airways.

Prognosis of SMA

SMA is a lifelong condition, and in many cases it is fatal.

The statistics suggest that most children with type 2 SMA will live fewer than six months, that most with type 2 SMA will live fewer than three years, and that most with type 3 SMA will not reach their thirties.

But those guidelines are based on historical data, and recent advances in medication and gene therapy have improved the outlook. It is currently unknown how much the new medications have improved the prognosis of SMA in the real world, but experts seem optimistic. Today, most doctors prefer not to make rigid predictions about life expectancy or weakness based on age of onset.

In types 3 and 4 SMA, lifespan should be unaffected, as the muscle weakness is unlikely to cause serious nutritional or respiratory problems.

Complications of SMA

SMA raises the risk of a number of health complications.

  • Nutritional and gastrointestinal conditions can develop because of the weakness of core muscles. When SMA progresses to an advanced state, swallowing difficulties can make eating challenging. Nutritional and gastrointestinal issues may include malnutrition, constipation, delayed gastric emptying, and potentially life-threatening gastroesophageal reflux with aspiration.

  • Respiratory and breathing problems also result from muscle weakness. People with advanced cases of SMA can have difficulty breathing or clearing their throat, raising a risk of pneumonia and respiratory failure. These complications are often the cause of death in people with SMA.

  • Orthopedic complications, including scoliosis, hip dislocation, and joint contractures, are common.

  • Metabolic complications, such as insulin resistance, hyperglycemia (high blood sugar), and high cholesterol, are common among adolescents with types 2 and 3 SMA, especially among those who cannot walk.

Research and Statistics: How Many People Have SMA?

About 1 in every 10,000 children is born with SMA.

SMA can affect pediatric and adult populations of all races and genders, but in North America it is about twice as common among white and Asian people as it is among African-American and Hispanic people.

Support for SMA

An SMA diagnosis (or the possibility of one) can be challenging for all family members. Children with SMA can require an immense amount of care, from both their families and medical professionals. Families seeking help have a number of resources to turn to.

Cure SMA is a national support program offering community and online support and information for all people with spinal muscular atrophy and their families. Most of Cure SMA’s resources are available at no cost.

mySMAteam is a social network for people with SMA and their loved ones.

The Muscular Dystrophy Association operates care centers across the country, linking patients with teams of specialists who work frequently with neuromuscular diseases.

The Takeaway

Spinal muscle atrophy (SMA), a neuromuscular condition usually diagnosed in children, can be an extremely serious condition, often leading to severe disability and early death. But recent advances in treating and managing SMA have improved the outlook for families by helping to expand lifespan and improve independence and quality of life.

Common Questions & Answers

What does SMA mean?
The words “spinal muscular atrophy” mean that the muscles, especially those near the spine, gradually weaken and waste away.
SMA is a genetic disease, and only occurs when both parents carry a rare genetic change in a gene that affects the nerves that control voluntary muscle movement.
SMA usually first appears as muscle weakness and low muscle tone in small children. These children will usually fail to hit developmental milestones, such as sitting up or standing.
While there is no cure for SMA, there are several newer treatments, all of which can deliver dramatic improvements to muscle strength and function.

Resources We Trust

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Anna-Hurst-bio

Anna C.E. Hurst, MD, MS, FACMG

Medical Reviewer
Anna C. E. Hurst, MD, is a medical geneticist with board certification in clinical genetics and pediatrics. She is an associate professor in the department of genetics at University of Alabama at Birmingham (UAB) and an adjunct faculty member at the HudsonAlpha Institute for Biotechnology. Prior to medical school, she received a master’s degree in genetic counseling, which inspired her interest in the communication of genetic information to patients and families with rare diseases.

Dr. Hurst is a physician for the UAB Undiagnosed Disease program, Turner syndrome clinic, and general genetics clinic, and she provides hospital consultations for inpatients at UAB and Children’s of Alabama for general genetics and inborn errors of metabolism. She also is the medical geneticist for the Smith Family Clinic for Genomic Medicine in Huntsville, Alabama.

Hurst's research focuses on expanding the availability of genomic sequencing for children with complex healthcare needs. She also has an interest in how the patient’s physical exam and facial features can be clues to a rare disease diagnosis (dysmorphology) and serves on the scientific advisory board of Facial Dysmorphology Novel Analysis. She has published over 45 peer-reviewed articles in the field of medical genetics, largely focused on the clinical delineation of rare disease phenotypes. She also serves as an associate editor for the American Journal of Medical Genetics.

Hurst is also passionate about education and serves as the program director of the UAB genetics residency programs (categorical, pediatrics-genetics, and internal medicine-genetics) and medical director of the UAB Genetic Counseling Training program. She is an officer with the Association of Professors in Human Medical Genetics.
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Hilary Macht is a New York City–based freelance writer covering health, science, and environment with a focus on the relationships among food, food culture, environment, and health. Her work has appeared in dozens of media outlets, including The New York Times, Columbia Journalism Review, Prevention, MORE, Essence, Civil Eats, EndocrineWeb, OnTrack Diabetes, and others, and is distributed by the National Center for Health Research and the Foundation for Informed Medical Decision Making.

Previously a senior editor at American Health for Women and health features editor at McCall’s, she’s been a frequent guest on national network and cable news shows including Today in New York (NBC), In Food Today (Food Network), CNBC, and others, and her groundbreaking story on Big Pharma and the media was featured on the CBS Evening News. She has a master's degree in science writing from the Columbia University Graduate School of Journalism.

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