Rare Medical News

Disease Profile

Spinal muscular atrophy 1

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

G12.0

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)

Werdnig-Hoffmann disease; Werdnig Hoffmann disease; Muscular atrophy, infantile;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Spinal muscular atrophy 1 (SMA1), also known as Werdnig Hoffmann disease, is a genetic neuromuscular disorder that affects the nerve cells that control voluntary muscles (motor neurons). Without treatment, symptoms of SMA1 become apparent before 6 months of age and include worsening muscle weakness and poor muscle tone (hypotonia) due to loss of the lower motor neurons in the spinal cord and brain stem. Feeding and breathing problems are also present.[1] SMA1 is caused by changes (pathogenic variants also called mutations) in the SMN1 gene and is typically inherited in an autosomal recessive manner.[1][2]

Diagnosis of SMA1 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 SMA1. Continued treatment with nusinersen is allowing many babies with SMA1 to reach and maintain age appropriate developmental milestones, including sitting, crawling, and walking. On average, breathing problems, nutrition problems, and hospital admissions have also decreased. However, response to treatment does vary. Some babies with SMA1 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

Infants with spinal muscular atrophy 1 (SMA1) experience severe weakness before 6 months of age. Muscle weakness, lack of motor development and poor muscle tone (hypotonia) are the major features of SMA1.[7][8] Infants with the poorest outlook have problems with breathing and feeding (sucking and/or swallowing).[2][7][8] Some children develop scoliosis (curvature of the spine) or other skeletal abnormalities. Intellectual development is usually normal.[8] Affected children are not able to sit up or stand, and the vast majority do not survive past 2 years of age due to respiratory failure.[2][9][8]

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
Areflexia
Absent tendon reflexes
0001284
Autosomal recessive inheritance
0000007
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
EMG: neuropathic changes
0003445
Proximal amyotrophy
Wasting of muscles near the body
0007126
Proximal muscle weakness in lower limbs
0008994
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Respiratory failure
0002878
Respiratory insufficiency
Respiratory impairment
0002093
Spinal muscular atrophy
Spinal muscle degeneration
Spinal muscle wasting

[ more ]

0007269
Tongue fasciculations
Tongue twitching
Twitching of the tongue

[ more ]

0001308
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629

Diagnosis

Genetic testing for spinal muscular atrophy 1 (SMA1) is available. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible, if the disease-causing mutations in the family have been identified. SMA1 is caused by mutations in the SMN1 gene, and extra copies of the SMN2 gene affect the severity of the condition.[11]

In some cases, interpreting results of carrier testing for SMA is difficult. Approximately 6% of parents of a child with SMA due to deletions in each copy of the gene have normal results of SMN1 dosage testing (carrier testing) for one of two reasons. Most people have one copy of SMN1 on each chromosome. However, about 4% of carriers have two copies of SMN1 on a single chromosome and a deletion on the other chromosome. These carriers with two copies of SMN1 on one chromosome are misdiagnosed as non-carriers by the SMN1 dosage test (they have a false negative test result). The second reason is that a new (de novo) deletion on one copy of the SMN1 gene occurs in 2% of people with SMA; in these cases, only one parent is a carrier.[11]

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. The genetics of SMA1 is complex. People with specific questions about genetic risks and genetic testing for themselves or family members should speak with a genetics professional.

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

    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.
        • MedlinePlus Genetics contains information on Spinal muscular atrophy 1. 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 1. 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 (GHR). January 2013; https://ghr.nlm.nih.gov/condition=spinalmuscularatrophy.
            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. Kaneshiro NK, Hoch DB. Spinal muscular atrophy. MedlinePlus. 2016; https://www.nlm.nih.gov/medlineplus/ency/article/000996.htm.
            8. Russman BS. Werdnig Hoffman Disease. National Organization for Rare Disorders (NORD). 2012; https://rarediseases.org/rare-diseases/werdnig-hoffmann-disease/.
            9. Motor Neuron Diseases Fact Sheet. National Institute of Neurological Disorders and Stroke (NINDS). 2012; https://www.ninds.nih.gov/disorders/motor_neuron_diseases/detail_motor_neuron_diseases.htm.
            10. Thomas W. Prior. Carrier screening for spinal muscular atrophy. Genetics in Medicine. November, 2008; 10(11):840-842.
            11. Prior TW & Russman BS. Spinal Muscular Atrophy. GeneReviews. November 14, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1352/.

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