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Spinal muscular atrophy

Reviewed September 2006

What is spinal muscular atrophy?

Spinal muscular atrophy is a disorder that affects the control of muscle movement. It is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). The loss of motor neurons leads to weakness and shrinkage (atrophy) of muscles used for activities such as crawling, walking, sitting up, and controlling head movement. In severe cases of spinal muscular atrophy, the muscles used for breathing and swallowing are affected.

Spinal muscular atrophy is divided into subtypes based on the severity and age of onset of symptoms. Three types of this disorder affect children before the age of 1 year. Type 0 is a very severe form of spinal muscular atrophy that begins before birth. Usually, the initial sign of type 0 is reduced movement of the fetus that is first noticed between 30 and 36 weeks of gestation. After birth, newborns show little movement and have difficulties swallowing and breathing. Type I spinal muscular atrophy (also called Werdnig-Hoffman disease) is a severe form of the disorder that is evident at birth or within the first few months of life. Typically, affected infants have difficulty breathing and swallowing, and they are unable to sit without support. Children with type II spinal muscular atrophy usually develop muscle weakness between ages 6 and 12 months. Children with type II can sit without support, although they cannot stand or walk unaided.

Type III spinal muscular atrophy (also called Kugelberg-Welander disease or juvenile type) is a milder form of the disorder than types 0, I or II. Symptoms appear between early childhood (older than age 1 year) and early adulthood. Individuals with type III spinal muscular atrophy can stand and walk unaided, but usually lose this ability later in life. Two types of spinal muscular atrophy, type IV and Finkel type, occur in adulthood, usually after age 30. Symptoms of adult-onset spinal muscular atrophy are typically mild to moderate and include muscle weakness, tremor, and twitching.

How common is spinal muscular atrophy?

Spinal muscular atrophy affects 1 in 6,000 to 1 in 10,000 people.

What genes are related to spinal muscular atrophy?

Mutations in the SMN1 and VAPB genes cause spinal muscular atrophy.

Extra copies of the SMN2 gene modify the course of spinal muscular atrophy.

Mutations in the SMN1 gene cause spinal muscular atrophy types 0, I, II, III, and IV. SMN1 mutations lead to a shortage of a protein, called SMN protein, which is needed for the survival of motor neurons. Without SMN protein, motor neurons die, and nerve impulses are not passed between the brain and muscles. As a result, some muscles cannot perform their normal functions, leading to weakness and impaired movement.

Some people with type II, III, or IV spinal muscular atrophy have three or more copies of the SMN2 genes in each cell. These multiple copies of the SMN2 gene can modify the course of spinal muscular atrophy. On a limited basis, extra SMN2 genes can help replace the shortage of SMN protein caused by mutations in the SMN1 genes. In general, symptoms are less severe and begin later in life as the number of copies of the SMN2 gene increases.

Finkel type spinal muscular atrophy is caused by a mutation in the VAPB gene. It is unclear how a VAPB mutation leads to the loss of motor neurons.

How do people inherit spinal muscular atrophy?

Spinal muscular atrophy types 0, I, II, III, and IV are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Finkel type spinal muscular atrophy is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Where can I find information about treatment for spinal muscular atrophy?

You may find information on treatment or management of spinal muscular atrophy or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about spinal muscular atrophy?

You may find the following resources about spinal muscular atrophy helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Spinal Muscular Atrophy (http://www.nlm.nih.gov/medlineplus/ency/article/000996.htm)
    • Health Topic: Spinal Muscular Atrophy (http://www.nlm.nih.gov/medlineplus/spinalmuscularatrophy.html)
  • Additional NIH Resources - National Institutes of Health
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.217)
    • National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/sma/sma.htm)
  • Educational resources - Information pages
    • Children's Hospital Boston (http://www.childrenshospital.org/az/Site1061/mainpageS1061P0.html)
    • Children's Hospital of The King's Daughters (http://www.chkd.org/HealthLibrary/content.aspx?pageid=P02623)
    • Madisons Foundation: Kugelberg-Welander spinal muscular atrophy (type III) (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,403/)
    • Madisons Foundation: Spinal Muscular Atrophy (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,203/)
    • Madisons Foundation: Werdnig-Hoffman disease (type I) (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,393/)
    • New York Online Access to Health (NOAH) (http://www.noah-health.org/en/bns/disorders/sp_disorder/specific/atrophy.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=70)
    • SMA Project (http://www.smaproject.org/)
  • Patient support - For patients and families
    • Claire Altman Heine Foundation (http://www.clairealtmanheinefoundation.org)
    • Families of Spinal Muscular Atrophy (http://www.fsma.org/booklet.shtml)
    • Genetic Alliance (http://www.geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=Kugelberg-Welander+Disease&expand=Treatment)
    • Muscular Dystrophy Association (http://www.mdausa.org/publications/fa-sma-qa.html)
    • National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Spinal+Muscular+Atrophy)
    • Spinal Muscular Atrophy Foundation (http://www.smafoundation.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sma)
  • Gene Tests - DNA tests ordered by healthcare professionals
    • Gene Tests: Spinal Muscular Atrophy (SMN1) (http://www.genetests.org/query?testid=2256)
    • Gene Tests: Spinal Muscular Atrophy (SMN2) (http://www.genetests.org/query?testid=270952)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22spinal+muscular+atrophy%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Muscular+Atrophy,+Spinal[MAJR])+AND+(spinal+muscular+atrophy[TI])+AND+review[pt]+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1800+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Spinal Muscular Atrophy (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=231)
  • OMIM - Genetic disorder catalog
    • OMIM: Spinal muscular atrophy, Finkel type (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182980)
    • OMIM: Spinal muscular atrophy, type I (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=253300)
    • OMIM: Spinal muscular atrophy, type II (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=253550)
    • OMIM: Spinal muscular atrophy, type III (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=253400)
    • OMIM: Spinal muscular atrophy, type IV (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=271150)

What other names do people use for spinal muscular atrophy?

  • hereditary motor neuronopathy
  • Progressive Muscular Atrophy
  • SMA

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about spinal muscular atrophy?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding spinal muscular atrophy?

atrophy ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; difficulty swallowing ; fetus ; gene ; juvenile ; motor ; motor neuron ; mutation ; nerve cell ; neuron ; protein ; recessive ; sign ; symptom ; tremor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Cifuentes-Diaz C, Frugier T, Melki J. Spinal muscular atrophy. Semin Pediatr Neurol. 2002 Jun;9(2):145-50. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12138998)
  • Gene Review: Spinal Muscular Atrophy (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sma)
  • Iannaccone ST, Smith SA, Simard LR. Spinal muscular atrophy. Curr Neurol Neurosci Rep. 2004 Jan;4(1):74-80. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14683633)
  • Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AH, Prior TW. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002 Jan-Feb;4(1):20-6. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11839954)
  • Monani UR. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron. 2005 Dec 22;48(6):885-96. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16364894)
  • Nicole S, Diaz CC, Frugier T, Melki J. Spinal muscular atrophy: recent advances and future prospects. Muscle Nerve. 2002 Jul;26(1):4-13. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12115944)
  • Nishimura AL, Mitne-Neto M, Silva HC, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JR, Gillingwater T, Webb J, Skehel P, Zatz M. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet. 2004 Nov;75(5):822-31. Epub 2004 Sep 15. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15372378)
  • Ogino S, Wilson RB. Genetic testing and risk assessment for spinal muscular atrophy (SMA). Hum Genet. 2002 Dec;111(6):477-500. Epub 2002 Oct 03. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12436240)
  • Ogino S, Wilson RB. Spinal muscular atrophy: molecular genetics and diagnostics. Expert Rev Mol Diagn. 2004 Jan;4(1):15-29. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14711346)
  • Prior TW, Swoboda KJ, Scott HD, Hejmanowski AQ. Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2. Am J Med Genet A. 2004 Oct 15;130(3):307-10. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15378550)
  • Talbot K, Davies KE. Spinal muscular atrophy. Semin Neurol. 2001 Jun;21(2):189-97. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11442327)
  • Wirth B, Brichta L, Schrank B, Lochmuller H, Blick S, Baasner A, Heller R. Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number. Hum Genet. 2006 May;119(4):422-8. Epub 2006 Mar 1. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16508748)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2006
Published: May 4, 2009