Spinal Muscular Atrophy

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Spinal Muscular Atrophy is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • SMA

Disorder Subdivisions

  • None

General Discussion

Spinal muscular atrophy (SMA) is a group of inherited disorders characterized by a loss of certain nerve cells in the spinal cord called motor neurons or anterior horn cells. Motor neurons receive the nerve impulses transmitted from the brain to the spinal cord (brainstem) and, in turn, transmit the impulses to the muscle via the peripheral nerves. The loss of motor neurons leads to progressive muscle weakness and muscle wasting (atrophy) in muscles closest to the trunk of the body (proximal muscles) such as the shoulders, hips and back. These muscles are necessary for crawling, walking, sitting up and head control. The more severe types of SMA can affect muscles involved in feeding, swallowing and breathing.

SMA is divided into subtypes based on age of onset and maximum function achieved. SMA types 0, 1, 2, 3 and 4 are inherited as autosomal recessive genetic disorders and are associated with abnormalities (mutations) in the SMN1 and SMA2 genes which are located on chromosome 5.


SMA type 0 is the most severe form of the disease and is characterized by decreased fetal movement, joint abnormalities, difficulty swallowing and respiratory failure.

SMA type 1 is the most common type of SMA and is also a severe form of the disease. Infants with SMA type 1 experience severe weakness before 6 months of age and never sit independently. Muscle weakness, lack of motor development and poor muscle tone are the major clinical manifestations of SMA type I. Infants with the gravest prognosis have problems sucking or swallowing. Some show abdominal breathing in the first few months of life. Muscle weakness occurs on both sides of the body and the ocular muscles are not affected. A twitching of the tongue is often seen. Intelligence is normal. Most affected children die before two years of age but survival may be dependent on the degree of respiratory function. For more information about SMA type 1, chose "Werdnig Hoffman" disease as your search term in the Rare Disease Database.

The onset of weakness in SMA type 2 patients is usually between 6 and 12 months. Affected children are able to sit independently early in development but are unable to walk even 10 feet independently. A trembling (tremor) of the fingers is almost always seen in SMA type 2. Approximately 70% of those affected do not have deep tendon reflexes. Those affected with SMA type 2 are usually not able to sit independently by the mid-teens or later.

Patients with SMA type 3 (Kugelberg-Welander syndrome) learn to walk but fall frequently and have trouble walking up and down stairs at 2-3 years of age. The legs are more severely affected than the arms. The long-term prognosis depends on the degree of motor function attained as a child. For more information about SMA3 chose "Kugelberg Welander syndrome" as your search term in the Rare Disease Database.

The onset of muscle weakness for those with SMA type 4 is after age 10 years; these patients usually are ambulatory until age 60 years.

Complications of SMA include scoliosis, joint contractures, pneumonia and metabolic abnormalities such as severe metabolic acidosis and dicarboxylic aciduria.


SMA types 0, 1, 2, 3 and 4 are inherited as autosomal recessive genetic disorders and are associated with abnormalities (mutations) in the SMN1 and SMA2 genes on chromosome 5 at chromosomal locus 5q11-q13. SMA1 is thought to be the primary disease-causing gene. Approximately 95-98% of affected individuals have deletions in the SMA1 gene and 2-5% have specific mutations in the SMA1 gene that result in a decreased production of the SMN protein. When three or more copies of the SMA2 gene are also present, the disease may be milder.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

Biological or surrogate markers for SMA are under development. These potential surrogate markers studied to date include:

1) Measuring the amount and ratio of full-length and truncated SMN2 RNA transcripts as well as the amount of SMN protein from white blood cells or fibroblast culture.

2) Counting motor units (Motor Unit Number Estimation, or MUNE) which have shown correlation with the SMN2 copy number, age, and function.

3) Quantitative ultrasound in assessing muscle changes in patients with SMA.

4) Electrical impedance myography.

5) The compound action potential determined by EMG in children with SMA. The authors point out that MUNE is difficult and not as reliable as initially thought. A longitudinally study of the surrogate markers will be necessary before any particular one can be used in an intervention study.

Affected Populations

The estimated frequency of spinal muscular atrophy is 1 in 4,000 to 1 in 7,000 people.

Standard Therapies


The diagnosis of SMA is suspected when symptoms are present and the diagnosis can be confirmed with molecular genetic testing. Molecular genetic testing is used to determine if a mutation is present in the SMN1 gene. SMA types 0, 1, 2, 3 and 4 are caused by a partial or complete loss of the SMN1 gene and about 95% of those affected will show a deletion of both copies of a specific portion (exon 7 or exon 8) of the gene. About 5% of those affected will show a deletion of exon 7 in one copy of the SMN1 gene and a different mutation in the other copy of the SMN1 gene. Molecular genetic testing can also be used to determine the number of copies of the SMN2 gene.

Prior to the availability of molecular testing, neurophysiologic studies and muscle biopsy were used for diagnosis, but these tests are no longer necessary unless SMN gene testing is normal.

Carrier testing for SMA is available using a molecular genetic test in which the number of copies of the SMN1 gene is determined.

Molecular genetic testing for the VAPB gene is available to diagnose Finkel type SMA.

Care for individuals with SMA is symptomatic and includes physical therapy, occupational therapy, monitoring of respiratory function and nutritional status, orthotics and adaptive equipment. Respiratory support for SMA1 using a breathing machine called BiPAP (bi-level positive airway pressure) has been shown to increase comfort and life expectancy in some affected children.

Genetic counseling is recommended for affected individuals and their families.


The management of children with spinal muscular atrophy starts with the diagnosis and

classification into 1 of the 5 categories. Health issues specific to spinal muscular atrophy are as follows:

Pulmonary management: Children with SMA1 can survive beyond 2 years

of age when offered tracheostomy or noninvasive respiratory support.

An intermittent positive-pressure breathing device (mechanical in-exsufflator) has proven effective.

Nutrition: Bulbar dysfunction is universal in SMA1 patients. Early gastrostomy should be

considered as part of the management of such patients. The bulbar dysfunction eventually

becomes a serious problem for spinal muscular atrophy II patients and only very late in the

course of disease for spinal muscular atrophy III patients.

Scoliosis: Scoliosis is a major problem in most SMA2 patients and in half of SMA3 patients.

The Vertical Expandable Prosthetic Titanium Rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. The titanium rib was developed at the University of Texas Health Science Center in San Antonio. It is manufactured by Synthes Spine Co.: http://www.synthes.com/sites/NA/Products/Spine/Screw_Hook_Rod_and_Clamp_System/Pages/VEPTR_and_VEPTR_II.aspx

For more information, please contact:

Synthes, Inc.

1302 Wrights Lane East

West Chester, PA 19380


Hip dislocation: Hip dislocation is another orthopedic concern in patients with spinal muscular atrophy. If the hip dislocation is asymptomatic, surgery is not indicated.

Behavior issues: Compared to siblings and normal controls, patients with spinal muscular

atrophy were quite well adjusted. Concern was, however, raised about unaffected siblings, who had a 2 to 3-fold higher rate behavioral problems than normal children.

Sleep disorders: Sleep-disordered breathing may develop prior to respiratory failure. Night-time use of continuous positive airway pressure with a nasal mask may be helpful.

Medication treatment: Specific medical treatments for spinal muscular atrophy do not exist. The following medications have studied and the results have been disappointing: Gabapentin, phenylbutyrate, valproic acid, hydroxyura, riluzole and myostatin.

Investigational Therapies

An open-label, escalating dose study to assess the safety, tolerability and dose-range finding of a single intrathecal dose of Isis 396443 in patients with spinal muscular atrophy has just commenced; the experimental drug has shown efficacy in the SMA mouse model.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:


Contact for additional information about spinal muscular atrophy:

Barry Russman, MD

Professor of Pediatrics and Neurology

Oregon Health Sciences University




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Brichta L, et al. Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet. 2003;12:2481-9.

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Laufersweiler-Plass C, Rudnik-Schöneborn S, Zerres K, Backes M, Lehmkuhl G, von Gontard A. Behavioural problems in children and adolescents with spinal muscular atrophy and their siblings. Dev Med Child Neurol. 2003;45(1):44-9.

Bromberg MB, Swoboda KJ. Motor unit number estimation in infants and children with spinal muscular atrophy. Muscle Nerve. 2002;25(3):445-7.

Courtens W, Johansson AB, Dachy B, Avni F, Telerman-Toppet N, Scheffer H. Infantile spinal muscular atrophy variant with congenital fractures in a female neonate: evidence for autosomal recessive inheritance. J Med Genet. 2002;39(1):74-7.

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Miller RG, Moore DH, Dronsky V, et al. A placebo-controlled trial of gabapentin in spinal muscular atrophy. J Neurol Sci. 2001;15;191(1-2):127-31.

Gozal D., Pulmonary manifestations of neuromuscular disease with special reference to Duchenne muscular dystrophy and spinal muscular atrophy. Pediatr Pulmonol. 2000;29:141-50.

Strober JB, et al., Progressive spinal muscular atrophies. J Child Neurol. 1999;14:691-95.

Andersson PB, et al., Neuromuscular disorders of childhood. Curr Opin Pediatr. 1999;11:497-503.

Liu YB, et al., Atrial standstill in a case of Kugelberg-Welander syndrome with cardiac involvement: an electrophysiologic study. Int J Cardiol. 1999;70:207-10.

Zerres K, Rudnick-Schoneborn S, Forrest E, et al. A collaborative study on the natural history of childhood and juvenile onset proximal SMA (type II and III SMA):569 patients. J Neurol Sci. 1997;146:67-72.

Cunha MC, et al., Spinal muscular atrophy type II (intermediary) and III (Kugelberg-Welander). Evolution of 50 patients with physiotherapy and hydrotherapy in a swimming pool. Arq Neuropsiquiatr. 1996;54:402-06.

Isozumi K, DeLong R, Kaplan J, et al. Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1-q24.31. Hum Mol Genet. 1996;5(9):1377-82.

Thomas NH, Dubowitz V. The natural history of type I (severe) SMA. Neuromuscular Disord. 1994;4:497-502.

Brzustowicz LM, et al., Assessment of non-allelic genetic heterogeneity of chronic (type II and III) spinal muscular atrophy. Hum Hered. 1993;43:380-87.

Miles JM, et al., Pathological case of the month. Type 3 spinal muscular atrophy (Kugelberg-Welander disease). Am J Dis Child. 1993;147:793-94.

Iannaccone ST, Browne RH, Samaha FL, et al. DCN/SMA group: A prospective study of SMA before age six years. Pediatr Neurol. 1993;9:187-193.

Russman BS, Iannaccone ST, Buncher CR, et al. New observations on the

natural history of SMA. J Child Neurol. 1992;7:347-353.

Fischbeck KH, Souders D, La Spada A. A candidate gene for X-linked spinal muscular atrophy. Adv Neurol. 1991;56:209-13.

Goutières F, Bogicevic D, Aicardi J. A predominantly cervical form of spinal muscular atrophy. J Neurol Neurosurg Psychiatry. 1991;54(3):223-5.

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Chou SM, Gilbert EF, Chun RW, et al. Infantile olivopontocerebellar atrophy with spinal muscular atrophy (infantile OPCA + SMA). Clin Neuropathol. 1990;9(1):21-32.

Urbanek K et al., ACTH and steroids in Kugelberg-Welander disease. Acta Univ Palacki Olomuc Fac Med. 1990;126:147-50.

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Prior TW, Russman BS. (Updated January 27, 2011). Spinal Muscular Atrophy. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1993-2012. Available at http://www.genetests.org. Accessed February 9, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spinal Muscular Atrophy, Type III; SMA3. Entry No: 253400. Last Edited November 15, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 9, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spinal Muscular Atrophy, Type I; SMA3. Entry No: 253300. Last Edited December 5, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 9, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spinal Muscular Atrophy, Type II; SMA2. Entry No: 253550. Last Edited July 26, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 9, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spinal Muscular Atrophy, Type IV; SMA4. Entry No: 271150. Last Edited August 21, 2007. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 9, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spinal Muscular Atrophy, Proximal, Adult, Autosomal Dominant. Entry No: 182980. Last Updated October 25, 2004. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 9, 2012.


March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Internet: http://www.marchofdimes.com

Cure SMA

925 Busse Road

Elk Grove Village, IL 60007

Tel: (847)367-7620

Tel: (800)886-1762

Email: info@cureSMA.org

Internet: http://www.cureSMA.org/

Muscular Dystrophy Association

3300 East Sunrise Drive

Tucson, AZ 85718-3208


Tel: (520)529-2000

Fax: (520)529-5300

Tel: (800)572-1717

Email: mda@mdausa.org

Internet: http://www.mda.org/

NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/

Jennifer Trust for Spinal Muscular Atrophy

40 Cygnet Court

Timothy's Bridge Road

Stratford upon Avon

Warwickshire, CV37 9NW

United Kingdom

Tel: 4401789267520

Fax: 4401789268371

Tel: 8009753100

Email: office@jtsma.org.uk

Internet: http://www.jtsma.org.uk

New Horizons Un-Limited, Inc.

811 East Wisconsin Ave

P.O. Box 510034

Milwaukee, WI 53203


Tel: (414)299-0124

Fax: (414)347-1977

Email: horizons@new-horizons.org

Internet: http://www.new-horizons.org

Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/

Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org

Fight SMA/Spinal Muscular Atrophy

1321 Duke Street

Suite 104

Alexandria, VA 22314

Tel: (703)299-1144

Email: CarolineGibson@fightsma.com

Internet: http://www.fightsma.org

Claire Altman Heine Foundation, Inc.

1112 Montana Avenue, #372

Santa Monica, CA 90403

Tel: (310)260-3262

Fax: (310)393-7154

Email: deb@preventsma.org

Internet: http://www.clairealtmanheinefoundation.org

Children with Spinal Muscular Atrophy Ukraine

Gogolia Street 7

Kharkiv, 61057


Tel: 380503640673

Email: info@csma.org.ua

Internet: http://www.csma.org.ua

Spinal Muscular Atrophy Foundation

888 Seventh Avenue

Suite 400

New York, NY 10019


Tel: (646)253-7100

Fax: (212)247-3079

Tel: (877)386-3762

Email: info@smafoundation.org

Internet: http://www.smafoundation.org

Child Neurology Foundation

201 Chicago Ave, #200

Minneapolis, MN 55415


Tel: (952)641-6100

Fax: (952)881-6276

Tel: (877)263-5430

Email: jstone@childneurologyfoundation.org

Internet: http://www.childneurologyfoundation.org

For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.