Connect with others who understand.

sign up log in
About mySMAteam

Spinal Muscular Atrophy – An Overview

Updated on April 27, 2021
Medically reviewed by
Evelyn O. Berman, M.D.
Article written by
Alison Channon

What Is Spinal Muscular Atrophy?

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder that causes muscle weakness and degeneration over time. There are five main types of SMA that account for 95 percent of cases – types 0, 1, 2, 3, and 4. 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 respiratory weakness, problems swallowing and chewing, lack of motor function, inability to walk, or mild muscle weakness.

Life expectancy is often reduced in more severe SMA types. The recent introduction of new therapies for SMA may influence the course of the disease, longevity, and disability.

What Causes SMA?

For SMA types 0-4, a person must inherit a mutated survival motor neuron 1 gene (SMN1) from each parent. The SMN1 gene, located on chromosome 5, is responsible for the production of survival motor neuron (SMN) protein. SMN protein is essential for the function of motor neurons – nerve cells that send signals from the brain and spinal cord to the muscles. If motor neurons can’t signal the muscles, the muscles atrophy. Depending on the severity of the SMA type, muscle atrophy can lead to compromised respiratory and motor function.

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 are caused by different gene mutations. Read more in Causes of Spinal Muscular Atrophy.

The History of Spinal Muscular Atrophy

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 types 3 or 4, were first described in the 1950s. The classification system used today to describe SMA types 0-4 was developed 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 mutated or deleted SMN1 gene. The same research team discovered the SMN2 gene, which is sometimes referred to as the SMA “back-up gene.”

Discovering the role of the SMN genes opened the door for new diagnostic tools and research. Before identifying 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. Improved understanding of the genetic pathology of SMA 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 – Spinraza (nusinersen). A second treatment for SMA in children under age 2, Zolgensma (onasemnogene abeparvovec-xioi), was approved in 2019.

How Common Is SMA?

SMA is a rare disease. It occurs in about 1 out of every 11,000 births in the United States. About 1 in 54 people in the U.S. is a carrier for SMA, though this rate varies by ethnic background. While SMA impacts a small number of people, it is the top genetic cause of infant mortality.

Types of SMA

There are five main types of SMA – types 0,1,2,3, and 4 – that comprise 95 percent of SMA cases. These types of SMA are all caused by a mutation on the SMN1 gene. Types 0-4 are differentiated by age of onset and severity.

  • Type 0 is among the rarest and severest forms of SMA. It affects babies before they’re born. Infants with type 0 have profound muscle weakness and significant breathing difficulties, which can severely curtail life expectancy.
  • Type 1, also called Werdnig-Hoffmann disease, comprises about 45 percent of all SMA cases. Type 1 usually impacts babies before they reach 6 months of age. Babies with type 1 have significant muscle weakness and problems breathing, sucking, and swallowing. Breathing problems contribute to a diminished lifespan – babies with type 1 SMA often do not live past age 2.
  • Type 2 accounts for about 20 percent of SMA cases. Symptoms generally appear in early childhood, between 6 months and 2 years old. Children with type 2 often develop the ability to sit up on their own but they rarely develop the ability to stand and do not develop the ability to walk. People with type 2 can live into young adulthood or longer with the right treatment and therapies.
  • Type 3 (Kugelberg-Welander disease) develops between 18 months and 30 years old. This less severe form of SMA accounts for 30 percent of cases. The first indications of SMA type 3 may be muscle weakness in the legs that causes falls and makes stair climbing difficult. Type 3 does not usually cause respiratory problems. While people with type 3 experience muscle degeneration, they have an average life expectancy.
  • Type 4 develops in adulthood, usually after age 35, and causes mild impairment. The first symptoms adults who develop type 4 may notice include tremors in the hands, a feeling of heaviness in the muscles, numbness, and muscle cramping. People with SMA type 4 have a normal life span and tend to remain mobile into their older age.

There are several other very rare types of SMA, including SMA with respiratory distress (SMARD) and distal SMA. Read more about types of spinal muscular atrophy.

How Is SMA Diagnosed?

Spinal muscular atrophy is usually diagnosed through genetic testing. The genetic test for SMA looks for mutations on the SMN1 gene on chromosome 5. Until recently, genetic testing was usually only conducted if a person showed symptoms of SMA or if there was a family history of the condition. Beginning in 2018, the United States Department of Health and Human Services added SMA to their list of conditions newborns should be screened for in their first 48 hours of life. As of January 2020, 17 states include SMA as part of routine newborn screening. Cure SMA offers resources for parents whose children were diagnosed through routine newborn screening.

Before genetic testing was available, SMA was diagnosed via a muscle biopsy. If SMA was suspected, doctors would remove a tiny piece of muscle tissue for evaluation in a lab and perform an electromyogram (EMG) to evaluate the electrical activity of muscles. Muscle biopsy and EMG may still be used on occasion if genetic testing is inconclusive.

Read more about genetic testing and spinal muscular atrophy diagnosis.

What Are the Symptoms of SMA?

Muscle weakness (hypotonia) is the primary symptom of every type of SMA. Muscle weakness can impact several functions.

Sucking, Chewing and Swallowing

Difficulty sucking, chewing, and swallowing are most prevalent in babies and children with severe forms of SMA. Eating difficulties are the result of muscle weakness in the throat and mouth. A feeding tube may be necessary to ensure infants and children with SMA receive adequate nutrition.

Motor Skills and Mobility

Motor skill development and mobility is depending on SMA type. Babies and children with SMA type 0 and type 1 will never develop the ability to sit up unsupported. Children with type 2 may learn to sit up but may lose that ability as SMA progresses.

Occasionally, children with SMA type 2 develop the ability to stand. Depending on age of onset, those with SMA type 3 can develop the ability to stand and walk, though these abilities may be compromised over time. Adults with type 4 generally only experience muscle weakness that impacts mobility in their older age.

Respiratory Function

Respiratory weakness can make it difficult for people with SMA to effectively cough to clear secretions from the lungs and can also put them at risk for aspiration. Inability to cough and aspiration increase the risk of chest infections like pneumonia.

Other Symptoms

There are many other SMA symptoms that can impact function and quality of life. They include:

  • Scoliosis (curvature of the spine)
  • Hand tremors
  • Tongue fasciculations (tongue quivering)
  • Joint contractures (joint shortening and tightening)
  • Bone fractures
  • Depression

Learn more about symptoms of spinal muscular atrophy.

How Is SMA Treated?

Depending on the type of SMA and symptoms, SMA can be treated with therapies that manage symptoms and disease-modifying therapies.

Disease-Modifying Therapies

There are two disease-modifying therapies available for SMA — Spinraza (nusinersen) and Zolgensma (onasemnogene abeparvovec-xioi). The FDA approved Spinraza in 2016 and Zolgensma in 2019. Both drugs are forms of gene therapy. People with SMA may be eligible to participate in clinical trials to receive access to new treatments.

Respiratory Support

Breathing support can be critical for people with more severe forms of SMA. Breathing problems can be addressed with noninvasive or invasive ventilation support. Noninvasive forms of ventilation support are used as needed and can be removed. A bilevel positive airway pressure (BiPAP) machine is a noninvasive option often used for breathing support while sleeping.

Ventilation supports that penetrate the body are available if noninvasive options aren’t sufficient. Examples include an endotracheal tube (tube that goes through the trachea to the lung) that can be used short-term and a tracheostomy (surgical placement of a breathing tube in the trachea). In addition to breathing support machines, respiratory therapy can help strengthen weak intercostal muscles.

Feeding Support

Feeding tubes may be necessary in cases where muscle weakness impacts a person’s ability to chew or swallow. Some feeding tubes are placed surgically through the skin and some are placed through the nose. They may go to the stomach or the small intestine.

Other Treatments

Condition Guide

References
  1. D'Amico, A., Mercuri, E., Tiziano, F. D., & Bertini, E. (2011). Spinal muscular atrophy. Orphanet Journal of Rare Diseases, 6(71).
  2. Kolb, S. J. (2011). Spinal Muscular Atrophy. Archives of Neurology, 68(8), 979–984. doi: 10.1001/archneurol.2011.74
  3. Spinal muscular atrophy. (2018, October). Retrieved December 20, 2019, from https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy
  4. Advances in Treatment of Spinal Muscular Atrophy – New Phenotypes, New Challenges, New Implications for Care https://content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd190424
  5. Spinal Muscular Atrophy. (n.d.). Retrieved December 20, 2019, from https://rarediseases.org/rare-diseases/spinal-muscular-atrophy/
  6. The Discovery of SMA. (2018, March 20). Retrieved December 30, 2019, from https://www.curesma.org/the-discovery-of-sma/
  7. Howell, K., Gibbs, R., & Rubin, L. L. (2019, March 18). Spinal Muscular Atrophy: Huge Steps. Retrieved January 2, 2019, from https://www.dana.org/article/spinal-muscular-atrophy-huge-steps/
  8. Food and Drug Administration. (2019, May 24). FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality [Press Release]. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease
  9. Sugarman, E. A., Nagan, N., Zhu, H., Akmaev, V. R., Zhou, Z., Rohlfs, E. M., … Allitto, B. A. (2011). Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72 400 specimens. European Journal of Human Genetics, 20(1), 27–32. doi: 10.1038/ejhg.2011.134
  10. Arnold, W. D., Kassar, D., & Kissel, J. T. (2014). Spinal muscular atrophy: Diagnosis and management in a new therapeutic era. Muscle & Nerve, 51(2), 157–167. doi: 10.1002/mus.24497
  11. Types of SMA. (2019, July 30). Retrieved December 20, 2019, from https://www.curesma.org/type-of-sma/
  12. Fujak, A., & Haaker, G. (2013). Proximal spinal muscular atrophy: current orthopedic perspective. The Application of Clinical Genetics, 113. doi: 10.2147/tacg.s53615
  13. Symptoms, Diagnosis & Effects of 5q SMA. (2019, March). Retrieved December 20, 2019, from https://smauk.org.uk/symptoms-diagnosis-effects-of-5q-sma
  14. Types of SMA: SMA linked to chromosome 5. (2019, September 20). Retrieved December 20, 2019, from https://www.mda.org/disease/spinal-muscular-atrophy/types
  15. Haelle, T. (2019, May 30). Spinal muscular atrophy added to newborn screening panel recommendations. Retrieved February 11, 2020, from https://www.mdedge.com/pediatrics/article/170539/neonatal-medicine/spinal-muscular-atrophy-added-newborn-screening-panel
  16. Conditions by State. (2020, January 24). Retrieved February 11, 2020, from https://www.babysfirsttest.org/newborn-screening/rusp-conditions#spinal-muscular-atrophy
  17. Medical Management. (2019, September 24). Retrieved January 6, 2020, from https://www.mda.org/disease/spinal-muscular-atrophy/medical-management
  18. Spinal Muscular Atrophy. (2015). Neurologic Clinics, 33(4), 831–846. doi: 10.1016/j.ncl.2015.07.004
  19. Schroth, M. K. (2019). Breathing Basics: Respiratory Care for Children with Spinal Muscular Atrophy. Elk Grove Village, IL: Cure SMA. https://www.curesma.org/wp-content/uploads/2019/07/breathing-basics.pdf
  20. Scoliosis in Spinal Muscular Atrophy - Spinal Muscular Atrophy UK. (n.d.). Retrieved December 30, 2019, from https://smauk.org.uk/scoliosis-in-spinal-muscular-atrophy
  21. Spinal Muscular Atrophy (SMA) Treatment. HM Insurance Group. PDF. (2019, June). Pittsburgh, PA. Retrieved January 2020, from https://www.hmig.com/wp-content/uploads/2019/06/pharmacy-focus-spinal-muscular-atrophy-treatment.pdf
  22. Spinal Muscular Atrophy in Adults - neuropt.org. (n.d.). Retrieved January 2020, from http://www.neuropt.org/docs/degenerative-diseases-sig/spinal-muscular-atrophy-in-adults.pdf?sfvrsn=8d2aae96_2
  23. Oleszek, J. L. (2019, November 12). Kugelberg Welander Spinal Muscular Atrophy Treatment & Management: Rehabilitation Program, Medical Issues/Complications, Surgical Intervention. Retrieved January 2020, from https://emedicine.medscape.com/article/306812-treatment#d9
  24. Scoliosis in SMA. SMA Foundation. (PDF) Retrieved January 2020, from https://www.smafoundation.org/wp-content/uploads/2014/03/Scoliosis-in-SMA.pdf
Evelyn O. Berman, M.D. is a neurology and pediatric specialist and treats disorders of the brain in children. Review provided by VeriMed Healthcare Network. Learn more about her 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.

Recent articles

Spinal muscular atrophy (SMA) is a disorder that leads to muscle weakness. People with this...

What Is the HINE-2 Motor Test for SMA?

Spinal muscular atrophy (SMA) is a disorder that leads to muscle weakness. People with this...
When diagnosing and treating pediatric spinal muscular atrophy (SMA), doctors need to understand...

What Is the CHOP INTEND Motor Test for SMA?

When diagnosing and treating pediatric spinal muscular atrophy (SMA), doctors need to understand...
Getting good nutrition on a daily basis can be a challenge for anyone. For those living with...

SMA Diet and Eating Tips

Getting good nutrition on a daily basis can be a challenge for anyone. For those living with...
Until very recently, treatments for spinal muscular atrophy (SMA) could only manage symptoms....

Treatments for Spinal Muscular Atrophy (SMA)

Until very recently, treatments for spinal muscular atrophy (SMA) could only manage symptoms....
Finkel type SMA (SMAFK) is a rare type of adult-onset (or late-onset) spinal muscular atrophy...

What Is Finkel Type SMA?

Finkel type SMA (SMAFK) is a rare type of adult-onset (or late-onset) spinal muscular atrophy...
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder that causes muscle weakness...

What Is the Hammersmith Functional Motor Scale for SMA?

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder that causes muscle weakness...
Spinal muscular atrophy with lower extremity predominance (SMA-LED) is a rare type of spinal...

What Is SMA-LED?

Spinal muscular atrophy with lower extremity predominance (SMA-LED) is a rare type of spinal...
With advances in genetics, invasive muscle biopsies are becoming less common in diagnosing spinal...

Is Muscle Biopsy Still Used to Diagnose SMA?

With advances in genetics, invasive muscle biopsies are becoming less common in diagnosing spinal...
Spinal muscular atrophy (SMA) is a rare genetic disease characterized by a deterioration of motor...

The Genetics of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a rare genetic disease characterized by a deterioration of motor...
Zebra fish are the ultimate study model animal for spinal muscular atrophy (SMA) because their...

Why the Zebra Fish? Understanding the SMA Study Model

Zebra fish are the ultimate study model animal for spinal muscular atrophy (SMA) because their...
mySMAteam My spinal muscular atrophy Team

Thank you for signing up.

close