National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Spinal muscular atrophy 1

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Other Names:
Werdnig-Hoffmann disease; Werdnig Hoffmann disease; Muscular atrophy, infantile; Werdnig-Hoffmann disease; Werdnig Hoffmann disease; Muscular atrophy, infantile; SMA1; SMA, infantile acute form; Proximal spinal muscular atrophy, type 1; Proximal spinal muscular atrophy type 1; SMA type 1; SMA type I; SMA-I See More
Categories:
This disease is grouped under:
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]
Last updated: 8/25/2018
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]
Last updated: 9/21/2016

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.

Showing of 12 |
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
Showing of 12 |
Last updated: 7/1/2020
Spinal muscular atrophy 1 (SMA1) is inherited in an autosomal recessive manner. This means that to be affected, a person must have a change (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 are typically unaffected and do not have any signs or symptoms of the condition.

When two carriers of an autosomal recessive condition have children, each child has a:
  • 25% chance to have the condition
  • 50% chance to be an unaffected carrier like each of the parents
  • 25% chance to not have the condition and not be a carrier.

An unaffected sibling of a person with SMA1 has a 2/3 chance to be a carrier.

Approximately 2% of cases of SMA1 are not inherited from both parents. In these cases, the affected person inherits one mutated copy of the gene from one carrier parent, and has a new mutation that occurs for the first time in the other copy of the gene.[10]

Last updated: 1/22/2015
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.
Last updated: 1/21/2015

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.

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.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include SMA2, congenital muscular dystrophies, congenital myopathies, some early-onset mitochondrial disorders, and carbohydrate metabolism disorders (see these terms).
Visit the Orphanet disease page for more information.

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 1. 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".

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

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

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). 
  • Genetics Home Reference (GHR) contains information on Spinal muscular atrophy 1. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • 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.

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.

  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; http://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; http://www.nlm.nih.gov/medlineplus/ency/article/000996.htm.
  8. Russman BS. Werdnig Hoffman Disease. National Organization for Rare Disorders (NORD). 2012; http://rarediseases.org/rare-diseases/werdnig-hoffmann-disease/.
  9. Motor Neuron Diseases Fact Sheet. National Institute of Neurological Disorders and Stroke (NINDS). 2012; http://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; http://www.ncbi.nlm.nih.gov/books/NBK1352/.