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Disease Profile

Spinal muscular atrophy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

SMA

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 trialsSMA 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]

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]

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.

    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.

    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

      Organizations Providing General Support

        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.

            References

            1. Learning About Spinal Muscular Atrophy. National Human Genome Research Institute. February 19, 2012; https://www.genome.gov/20519681/.
            2. Spinal muscular atrophy. MedlinePlus. November 22, 2017; https://medlineplus.gov/ency/article/000996.htm.
            3. Russman B. Spinal Muscular Atrophy. National Organization for Rare Disorders (NORD). 2012; https://rarediseases.org/rare-diseases/spinal-muscular-atrophy/.
            4. Spinal muscular atrophy. Genetics Home Reference (GHR). January 2013; https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy.
            5. 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.
            6. 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.
            7. 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.
            8. 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.
            9. Addison F. SMA Added to List of Recommended Screenings for Disease Given to Newborns in US. Frontline Genomics. July 6, 2018; https://www.frontlinegenomics.com/news/24542/sma-test-added-to-newborn-screening-recommendations/.
            10. Thomas W Prior, PhD, FACMG and Barry S Russman, MD. Spinal Muscular Atrophy. GeneReviews. November 2013; https://www.ncbi.nlm.nih.gov/books/NBK1352/.
            11. Kao A. Spinal Muscular Atrophy. Medscape Reference. January 4 2017; https://emedicine.medscape.com/article/1181436-overview.

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