Spinal muscular atrophy

Información en español Title

Other Names:

SMA

Subtypes:

Spinal muscular atrophy 1; Spinal muscular atrophy Ryukyuan type; Spinal muscular atrophy type 1 with congenital bone fractures; Spinal muscular atrophy 1; Spinal muscular atrophy Ryukyuan type; Spinal muscular atrophy type 1 with congenital bone fractures; Spinal muscular atrophy type 2; Spinal muscular atrophy type 3; Spinal muscular atrophy type 4; Spinal muscular atrophy with respiratory distress 1 See More

Summary Summary

Spinal muscular atrophy (SMA) is a group of genetic neuromuscular disorders that affect the nerve cells that control voluntary muscles (motor neurons). The loss of motor neurons causes progressive muscle weakness and loss of movement due to muscle wasting (atrophy). The severity of the symptoms, the age at which symptoms, begin, and genetic cause varies by type. Many types of SMA mainly affect the muscles involved in walking, sitting, arm movement, and head control. Breathing and swallowing may also become difficult as the disease progresses in many types of SMA. In some types of SMA, the loss of motor neurons makes it hard to control movement of the hands and feet.^[1]^[2]^[3]

SMA type 1, 2, 3, and 4 are caused by changes (pathogenic variants, also know as mutations) in the SMN1 gene and are inherited in an autosomal recessive manner. Extra copies of the nearby related gene, SMN2, modify the severity of SMA. There are other rarer types of SMA caused by changes in different genes. Other autosomal recessive forms include SMA with progressive myoclonic epilepsy (SMA-PME) caused by changes in the ASAH1 gene and SMA with respiratory distress 1 (SMARD1) caused by changes in the IGHMBP2 gene. Autosomal dominant forms include distal MSA type V (DSMA-V) caused by changes in BSCL2 and GARS, SMA with lower extremity predominance (SMA-LED) caused by changes in DYNC1H1 or BICD2, and adult-onset form of SMA caused changes by VAPB. X-linked forms include X-linked infantile SMA caused by changes in UBA1.^[4]

Diagnosis of SMA is suspected by symptoms and confirmed by genetic testing. Treatments are in general supportive aiming to increase quality of life and avoid complications. Treatments may include physical therapy, nutrition support, chest physiotherapy, and, in severe cases, breathing machines (ventilators).^[5]^[6] In December 2016, nusinersen (Spinraza) became the first FDA approved treatment for SMA types 1, 2, 3, and 4. Continued treatment with nusinersen has been shown to slow the progression of the disease and even improve muscle function, but individual response to the treatment does vary.^[7]^[8] Due to the success of nusinersen as well as other promising treatments presently in clinical trials, SMA caused by changes in the SMN1 gene has been added to the list of recommended newborn screening tests in the United States, so that treatment may begin before symptoms develop. However, as of July 2018, not all States have added the test to their newborn screening panel.^[9]

Last updated: 8/25/2018

Symptoms Symptoms

Spinal muscular atrophy (SMA) is primarily characterized by progressive muscle weakness and atrophy. Depending on the type, onset may range from before birth to adolescence or young adulthood.^[10]

SMA type 0 (the prenatal form) is the most severe form and begins before birth. Usually, the first symptom of type 0 is reduced movement of the fetus that is first seen between 30 and 36 weeks of the pregnancy. After birth, these newborns have little movement and have difficulties with swallowing and breathing.^[1] Life span is approximately 2-6 months.^[10]

There are 3 types of SMA that tend to affect children before the age of one (SMA type I, SMA type II, and X-linked SMA). SMA type 1 is a severe form that may be apparent at birth or the first few months of life. Features may include difficulty swallowing or breathing and inability to sit without support.^[4] The life span is usually less than 2 years.^[10] SMA type II typically becomes apparent between 6 and 12 months of age; affected children may sit without support, although they cannot stand or walk unaided.^[4] About 70% of people with this type live to be at least 25 years of age.^[10] X-linked infantile SMA is similar to SMA type I; additional features may include joint deformities (contractures) or even broken bones at birth in very severe cases.^[4]

Three other types of SMA can affect people in early childhood and adulthood.^[4] SMA type III (also called Kugelberg-Welander disease or juvenile type) is a milder form of spinal muscular atrophy with symptoms that generally appear between early childhood (older than age 1 year) and early adulthood. People with type III are able to stand and walk without help, although they usually lose this ability later in life.^[1] SMA type IV and Finkel type occur in adulthood, usually after age 30. Symptoms of adult-onset SMA are usually mild to moderate and include muscle weakness, tremor and twitching.^[1]

Last updated: 1/7/2016

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Inheritance Inheritance

Most forms of spinal muscular atrophy (types I, II, III, and IV, specifically) are inherited in an autosomal recessive pattern.^[4] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Finkel type spinal muscular atrophy is inherited in an autosomal dominant pattern, which means an affected person only needs a mutation in one copy of the responsible gene in each cell.^[4]

X-linked infantile spinal muscular atrophy is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.^[4]

Last updated: 1/7/2016

Treatment Treatment

Treatment for SMA may vary depending on the subtype of SMA and severity of symptoms, but generally focuses on supportive care to increase the person's quality of life. In general, treatment may include physical therapy and assistive equipment to increase mobility, such as leg braces, walkers, and wheelchairs. Back braces may be used to assist sitting and prevent scoliosis and other complications affecting the backbone. Special breathing exercises, cough machines, and chest physiotherapy can help maintain the function of the lungs and keep the airways clear of mucous, especially in times of illness. A dietitian may help support nutrition if eating or swallowing becomes difficult.^[5]^[6]

For SMA types 1, 2, 3, and 4, nusinersen (Spinraza) is the first and only FDA approved treatment. Continued treatment with nusinersen has been found to increase motor function and slow the progression of symptoms. Many babies and young children with types 1 and 2 are able to reach developmental milestones and maintain those milestones over time. In general, breathing problems, nutrition problems, and hospital admissions also decrease. Older children with type 3 and adults with type 4 have also been shown to benefit from continuous treatment with nusinersen, including, for some, regaining the ability to walk longer distances, improving arm movement, and slowing or stopping the progression of the disorder. Ongoing, long term medical studies continue to report improvements. However, response to treatment does vary and some people with SMA types 1, 2, 3, or 4 may not respond to the drug at all or may have medical complications that prevent use of the treatment.^[7]^[8]

Cure SMA has more detailed information about the management of medical issues associated with SMA. Their webpage includes hyperlinks to the latest published consensus medical guidelines (2018) for SMA treatment to share with the doctors involved in the care of the person with SMA.

CureSMA: Living with SMA Medical Issues

Last updated: 8/25/2018

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Risdiplam (Brand name: Evrysdi) - Manufactured by Genentech
FDA-approved indication: August 2020, risdiplam (Evrysdi) was approved for the treatment of spinal muscular atrophy (SMA) in patients 2 months of age and older.
National Library of Medicine Drug Information Portal
Nusinersen (Brand name: Spinraza) - Manufactured by Biogen, Inc
FDA-approved indication: December 2016, nusinersen (Spinraza) was approved for the treatment of spinal muscular atrophy in pediatric and adult patients.
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Onasemnogene abeparvovec (Brand name: Zolgensma) - Manufactured by AveXis, Inc.
FDA-approved indication: May 2019, onasemnogene abeparvovec (Zolgensma) was approved for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
National Library of Medicine Drug Information Portal

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Spinal muscular atrophy. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Cure SMA
925 Busse Road
Elk Grove, IL 60007
Toll-free: 800-886-1762
Telephone: 847-367-7620
Fax: 847-367-7623
E-mail: info@curesma.org
Website: http://www.curesma.org
Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 1-833-275-6321 (Helpline)
E-mail: resourcecenter@mdausa.org
Website: https://www.mda.org
SMA Europe
Europe,
Telephone: +44 (0)1789 801159
E-mail: vanessa@sma-europe.eu
Website: http://www.sma-europe.eu/
SMA Gruba
Turkey
Telephone: 0535 715 3781
E-mail: smagruba-iletisim@hotmail.com
Website: http://smagrubu.net/
Spinal Muscular Atrophy Association of Australia Inc. (SMA Australia)
PO Box 5245 (mail)
Unit 7 16-28 Melverton Drive (office)
Hallam Vic, 3803 Australia
Telephone: (03) 9796 5744
Fax: 03 83737 7787
E-mail: smaaa@smaaustralia.org.au
Website: http://smaaustralia.org.au/
Spinal Muscular Atrophy Foundation
888 Seventh Avenue
Suite 400
New York, NY 10019
Toll-free: 877-FUND-SMA (877-386-3762)
Telephone: 646-253-7100
Fax: 212-247-3079
E-mail: info@smafoundation.org
Website: http://www.smafoundation.org

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Cure SMA, an organization dedicated to the treatment of SMA and providing families with support, provides information about the types, causes and diagnosis of SMA.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
Genetics Home Reference (GHR) contains information on Spinal muscular atrophy. This website is maintained by the National Library of Medicine.
The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

SMArt Moves, a disease awareness and educational campaign launched by Cure SMA, provides resources for parents, pediatricians and other healthcare professionals to promptly recognize and diagnose the early signs of spinal muscular atrophy (SMA). SMArt Moves has an SMA Diagnostic Toolkit to help healthcare professionals recognize SMA in their patients.
GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
PubMed is a searchable database of medical literature and lists journal articles that discuss Spinal muscular atrophy. Click on the link to view a sample search on this topic.

News & Events News & Events

News

NORD RareLaunch® Workshops
December 1, 2020
Rare Diseases Are Not Rare - Gallery of Creative Work Raises Awareness of Rare Diseases
September 1, 2020
NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020
FDA Approves Innovative Gene Therapy to Treat Pediatric Patients with Spinal Muscular Atrophy
July 30, 2019

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

If members of a couple are carriers of SMA and had a baby affected with SMA type 1, is there a chance that they could have babies affected with other types of SMA or it will always be the same type that would appear in their children? See answer
Are there any other diseases or conditions that have similar symptoms to SMA, or mimic the symptoms of SMA? See answer

Have a question? Contact a GARD Information Specialist.

References References

Learning About Spinal Muscular Atrophy. National Human Genome Research Institute. February 19, 2012; https://www.genome.gov/20519681/.
Spinal muscular atrophy. MedlinePlus. November 22, 2017; https://medlineplus.gov/ency/article/000996.htm.
Russman B. Spinal Muscular Atrophy. National Organization for Rare Disorders (NORD). 2012; https://rarediseases.org/rare-diseases/spinal-muscular-atrophy/.
Spinal muscular atrophy. Genetics Home Reference (GHR). January 2013; https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy.
Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. February 2018; 28(2):103-115. https://www.sciencedirect.com/science/article/pii/S0960896617312841?via%3Dihub.
Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. March 2018; 28(3):197-207. https://www.sciencedirect.com/science/article/pii/S0960896617312907?via%3Dihub.
Kariyawasam D, Carey KA, Jones KJ, Farrar MA. New and developing therapies in spinal muscular atrophy. Paediatr Respir Rev. April 5, 2018; pii: S1526-0542(18):30048-4. https://www.ncbi.nlm.nih.gov/pubmed/29703692.
Claborn MK, Stevens DL, Walker CK, Gildon BL. Nusinersen: A Treatment for Spinal Muscular Atrophy. Ann Pharmacother. July 1, 2018; 1060028018789956. https://www.ncbi.nlm.nih.gov/pubmed/30008228.
Addison F. SMA Added to List of Recommended Screenings for Disease Given to Newborns in US. Frontline Genomics. July 6, 2018; http://www.frontlinegenomics.com/news/24542/sma-test-added-to-newborn-screening-recommendations/.
Thomas W Prior, PhD, FACMG and Barry S Russman, MD. Spinal Muscular Atrophy. GeneReviews. November 2013; http://www.ncbi.nlm.nih.gov/books/NBK1352/.
Kao A. Spinal Muscular Atrophy. Medscape Reference. January 4 2017; https://emedicine.medscape.com/article/1181436-overview.