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Disease Profile

Spinal muscular atrophy type 2

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

G12.1

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)

SMA2; Muscular atrophy, spinal, intermediate type; Muscular atrophy, spinal, infantile chronic form;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Spinal muscular atrophy type 2 (SMA2) is a genetic neuromuscular disorder that affects the nerve cells that control voluntary muscles (motor neurons). Without treatment, progressive muscle weakness develops in babies with SMA2 between ages 6 and 12 months. Babies with SMA2 can sit without support, however, they cannot stand or walk independently. Feeding and breathing problems also develop.[1] SMA2 is caused by changes (pathogenic variants also called mutations) in the SMN1 gene and is inherited in an autosomal recessive manner.[1][2]

Diagnosis of SMA2 is suspected by symptoms and confirmed by genetic testing. SMA has been added to the list of recommended newborn screening tests in the United States, so that it can be detected prior to symptoms developing. This occurred because treatments are being developed that are changing the course of the disease. In December 2016, nusinersen (Spinraza) became the first FDA approved treatment for SMA2. Continued treatment with nusinersen is allowing many babies and children with SMA2 to reach and maintain age appropriate developmental milestones, including sitting, crawling, and walking. Breathing problems, nutrition problems, and hospital admissions also decrease in general. However, response to treatment does vary. Some children with SMA2 may not respond to the nusinersen at all or may have medical complications that prevent use of the treatment.[3][4] Other treatments remain supportive.[5][6]

Symptoms

The signs and symptoms of spinal muscular atrophy type 2 (SMA II) typically become apparent between 6 and 12 months of age. Poor muscle tone may be noticed at birth or within the first few months of life. Affected children may initially slowly gain some motor milestones. However, the highest motor milestone attained is generally the ability to sit independently, and this milestone is often lost by the mid-teens. People with SMA II are not able to stand or walk unaided. Other signs and symptoms may include a tremor of the fingers, breathing issues, feeding difficulties and skeletal abnormalities (such as scoliosis and hip dislocation).[7]

For information about the signs and symptoms of spinal muscular atrophy in general, click here.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Degeneration of anterior horn cells
0002398
EMG abnormality
0003457
Hand tremor
Tremor of hand
Tremor of hands
tremors in hands

[ more ]

0002378
Muscle weakness
Muscular weakness
0001324
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Spinal muscular atrophy
Spinal muscle degeneration
Spinal muscle wasting

[ more ]

0007269
Tongue fasciculations
Tongue twitching
Twitching of the tongue

[ more ]

0001308

Cause

Spinal muscular atrophy type 2 (SMA II) is caused by changes (mutations) in the SMN1 gene. Extra copies of the SMN2 gene affect how severe the condition is. These genes encode a protein that is important for the normal functioning of certain nerve cells (called motor neurons) which help control muscle movements. Mutations in the SMN1 gene lead to reduced levels of this protein and the death of motor neurons. This in turn causes the characteristic signs and symptoms associated with SMA II.[2]

The protein made by additional copies of SMN2 can compensate for some of the protein lost due to mutations in SMN1. Affected people who have extra copies of SMN2 may, therefore, have milder symptoms and develop the condition later in life.[2]

Diagnosis

A diagnosis of spinal muscular atrophy (SMA) is first suspected based on the presence of characteristic signs and symptoms. Identifying mutations in the SMN1 gene confirms the diagnosis.[7]

Classifying the type of SMA is based on the age of onset and the maximum function attained. Classisfying SMA as type 2 is based on:

  • onset of muscle weakness usually after age six months; ability to sit independently achieved when placed in a sitting position
  • finger trembling almost invariably present
  • low muscle tone (flaccidity)
  • absence of tendon reflexes in approximately 70% of individuals
  • average intellectual skills during the formative years and above average by adolescence

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    The treatment of spinal muscular atrophy type 2 (SMA2) may include nusinersen (Spinraza). Nusinersen is injected into the fluid-filled space of the spinal canal. After the initial 4 doses which are given close together, nusinersen is given once every 4 months. The treatment works by increasing the amount of working SMN protein made by the SMN2 gene. Continued treatment with nusinersen has been reported to dramatically slow progression of the disease and has in some cases improved symptoms already present. Best results have been reported when the treatment is started before symptoms begin. Ongoing studies are focused on determining the long term effectiveness of nusinersen and continue to look promising. However, not all children with SMA2 respond to treatment with nusinersen. In addition, certain medical complications may prevent the use of the treatment.[4]

    Depending on timing and response to treatment, supportive treatment may include physical therapy, occupational therapy and assistive devices (braces, walkers, wheelchairs, etc) to maximize mobility and independence. These therapies may also prevent or delay scoliosis and abnormal contractions of the muscles and tendons. Some children with SMA2 may have difficulty eating enough calories to maintain a normal weight. In these cases, nutritional counseling and/or a feeding tube may become necessary. If necessary, breathing may be supported by the use of BiPAP machines or other methods of respiratory support. Some children with SMA2 may require surgery to treat scoliosis or severe cases of hip dislocation.[5][6]

    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

        • Families of SMA has created a booklet entitled Understanding SMA that is intended to serve as a source of information and support for children and adults with Spinal Muscular Atrophy (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 type 2. This website is maintained by the National Library of Medicine.
        • 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

          • 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.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Spinal muscular atrophy type 2. Click on the link to view a sample search on this topic.

            References

            1. Prior TW, Finanger. Spinal Muscular Atrophy. GeneReviews. December 22, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1352/.
            2. Spinal Muscular Atrophy. Genetics Home Reference. January 2013; https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy.
            3. 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.
            4. 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.
            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. Thomas W Prior, PhD, FACMG and Barry S Russman, MD. Spinal Muscular Atrophy. GeneReviews. November 2013; https://www.ncbi.nlm.nih.gov/books/NBK1352/.
            8. Bryan Tsao. Spinal Muscular Atrophy. Medscape Reference. 2015; https://emedicine.medscape.com/article/1181436-overview.

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