Spinal Muscular Atrophy - NORD (National Organization for Rare Disorders) (2022)

Spinal Muscular Atrophy

NORD gratefully acknowledges Etienne Leveille, MD, Yale School of Medicine, and Mary Schroth, MD, FAAP, FCCP, Chief Medical Officer, Cure SMA, for assistance in the preparation of this report.

Synonyms of Spinal Muscular Atrophy

  • SMA

Subdivisions of Spinal Muscular Atrophy

  • SMA type 0 (prenatal SMA)
  • SMA type 1 (infantile SMA, Werdnig-Hoffmann disease)
  • SMA type 2 (intermediate SMA, Dubowitz disease)
  • SMA type 3 (juvenile SMA, Kugelberg-Welander disease)
  • SMA type 4 (late onset SMA

General Discussion

Spinal muscular atrophy (SMA) is a group of inherited neuromuscular disorders characterized by loss of nerve cells in the spinal cord called lower motor neurons or anterior horn cells. Lower motor neurons originate in the brainstem or the spinal cord and relay nerve impulses from upper motor neurons, located in the brain, to the muscles they control. The loss of lower motor neurons leads to progressive muscle weakness, muscle wasting (atrophy) and low muscle tone (hypotonia) that is typically more pronounced in muscles closest to the trunk of the body (proximal muscles) such as the shoulders, hips and back. However, neurons controlling most voluntary muscles can be affected, including those that control muscles involved in feeding, swallowing and breathing.

SMA is divided into subtypes (SMA types 0 to 4) based on age of symptom onset and maximum motor function achieved, with a lower number representing a younger age of onset and more severe disease. SMA is inherited as an autosomal recessive genetic disorder and is associated with mutations in the survivor motor neuron 1 (SMN1) gene. SMN1 is located on chromosome 5 in the long arm (q) region. Thus, SMA with a SMN1 gene deletion is often referred to as 5q SMA, distinguishing this form of SMA from other genetic forms of SMA.

Newborn screening facilitates early identification of infants with SMA and thus early implementation of treatment. Infants identified by SMA newborn screening are urgently referred for confirmatory testing, discussion of treatments and care. Early treatment prior to the onset of symptoms provides the best outcomes.

Although the management of SMA was previously centered around symptom management and supportive care, since 2016, therapies that can improve the course of the disease (disease-modifying therapies) have emerged and have shown promising results. Currently three SMN-enhancing treatments have U.S. Food and Drug Administration (FDA) approval.

Signs & Symptoms

The signs and symptoms of SMA are a consequence of lower motor neuron loss. The features of lower motor neuron disease include muscle weakness and atrophy, hypotonia, decreased or absent reflexes (hypo- or areflexia) and twitching of muscle fibers (fasciculations). Although SMA is a disease spectrum, the five subtypes are determined based on their age of symptom onset and maximum motor function achieved. This classification for SMA was established prior to the availability of genetic testing and prior to the availability of disease modifying treatments.

SMA type 0, also known as prenatal SMA, is the most severe form of the disease and develops before birth. The first sign may be a decrease or loss of fetal movement during late pregnancy. Symptoms of SMA type 0 are apparent at birth and include severe weakness and hypotonia. In addition, joint deformity and tightening (contractures) and congenital heart defects are common. As a result, infants do not achieve developmental motor milestones. Because of severe respiratory muscle weakness, affected infants rapidly progress to respiratory failure often by the first month of life.

SMA type 1, also known as infantile SMA or Werdnig-Hoffmann disease, is the most common type of SMA affecting approximately 60% of infants born with SMA and is also a severe form of the disease. Infants with SMA type 1 usually appear normal at birth but experience severe weakness before 6 months of age. Developmentally they do not achieve independent sitting and may achieve very few developmental motor milestones. Because of lower motor neuron loss, affected infants have poor suck and swallow reflexes and respiratory muscle weakness. Historically without intervention, affected children die before two years of age due to progressive respiratory muscle weakness and respiratory failure.

SMA type 2, also known as intermediate SMA or Dubowitz disease, comprises about 30% of infants born with SMA. The disease usually manifests between 6 and 18 months of age. Affected children can sit independently at some point in their development. However, this ability is usually lost by the mid-teens or later and affected individuals never achieve independent standing and walking. Additional associated symptoms include difficulty swallowing (dysphagia) and respiratory difficulties. Trembling (tremor) of the fingers is also common. In addition, weakness of the muscles supporting the spine leads to curvature of the spine (scoliosis). Historically, life expectancy is reduced in patients with SMA type 2 but many reach adulthood.

SMA type 3, also known as juvenile SMA or Kugelberg-Welander disease, accounts for about 10% of infants born with SMA. The age of onset is variable and can be as early as 18 months or as late as teenage years. Although affected individuals have hip and leg weakness and may fall frequently, they are able to walk independently at some point in their development. However, the ability to walk and stand may be lost as they grow and with disease progression, and many become wheelchair dependent. Long-term prognosis depends on the degree of motor function attained as a child, and respiratory muscle weakness is typically mild or absent. SMA type 3 is associated with a normal life expectancy.

SMA type 4, also known as late-onset SMA, occurs in less than 1% of people with SMA. Symptoms are less severe than in other subtypes and onset typically occurs in adulthood and most commonly after 35 years of age. All motor developmental milestones are achieved and most individuals with SMA type 4 can walk throughout their life. Patients with SMA type 4 have a normal life expectancy.

The following resources from Cure SMA provides a description of symptoms, as well as videos to assist with early diagnosis:

https://smartmoves.curesma.org/

https://www.curesma.org/types-of-sma/

Causes

SMA is caused by deletion or mutation in the SMN1 gene, which encodes a protein known as survival motor neuron (SMN). This protein plays an important role in the functioning and maintenance of motor neurons. Approximately 95-98% of affected individuals have deletions in the SMN1 gene and 2-5% have a point mutation in the SMN1 gene that results in a decreased production of the SMN protein.

The SMN2 gene is a paralog of SMN1 and also encodes the SMN protein and can partially compensate for the loss of the SMN1 gene. However, most SMN protein produced by the SMN2 gene is not functional, which means that the SMN2 gene can only partially compensate for the loss of the SMN1 gene. For this reason, an individual with SMA who has more copies of the SMN2 gene will produce more functional SMN protein and may be better able to compensate for the loss of the SMN1 gene, therefore leading to less severe disease. Generally, more copies of SMN2 are associated with milder SMA disease, although there are exceptions.

SMA is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a pathogenic gene variant for the disease from each parent. If an individual receives one normal gene and one variant 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 variant 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 is 25%. The risk is the same for males and females.

Parents who are close blood relative (consanguineous) are more likely to have the same harmful gene variant and, therefore, to have an affected child.

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Affected Populations

The incidence of SMA is approximately 1 in 10,000 live births. SMA affects females and males equally.

Related Disorders

Symptoms of the following disorders can be similar to those of SMA. Comparisons may be useful for a differential diagnosis.

Several other forms of SMA exist beyond those caused by anomalies in the SMN1 gene. These other forms of SMA affect lower motor neurons, although they might preferentially affect certain parts of the body and may be associated with other symptoms. These types of SMA notably include scapuloperoneal SMA, SMA with pontocerebellar hypoplasia, X-linked infantile SMA with arthrogryposis, SMA with respiratory distress type I (SMARD1), congenital distal SMA, distal SMA-V/CMT2d and Finkel type SMA.

Congenital myasthenic syndromes are caused by genetic defects of muscle and nerve communication (neuromuscular transmission). These conditions usually occur in infants but may become evident in adulthood. Associated features may vary in severity from person to person. Symptoms may include feeding difficulties, sudden episodes of absence of spontaneous breathing (apnea), failure to grow and gain weight at the expected rate (failure to thrive), muscle weakness and fatigue, weakness or paralysis of eye muscles (ophthalmoplegia) and other abnormalities. (For more information on these disorders, choose “Congenital Myasthenic Syndromes” as your search term in the Rare Disease Database.)

Congenital myopathies are a group of inherited diseases that affect the muscles (myopathy) and are characterized by weakness and hypotonia, often present at birth. There are several different subtypes of congenital myopathies, and many are caused by pathogenic variants in specific genes. They differ in severity and onset of symptoms, cellular characteristics under a microscope and prognosis. Symptoms can be present from birth or slowly progress throughout infancy and childhood, but these disorders do not typically get more severe in adulthood. (For more information on these disorders, choose “Congenital Myopathy” as your search term in the Rare Disease Database.)

Congenital muscular dystrophy (CMD) is a general term for another group of genetic muscle diseases that occur at birth or early during infancy. CMDs are generally characterized by hypotonia, progressive muscle weakness and atrophy, contractures, spinal rigidity and delays in reaching motor milestones. Feeding difficulties and respiratory complications can develop in some patients. Muscle weakness may improve, remain stable or worsen. Some forms of CMD may be associated with structural brain abnormalities and intellectual disability. The severity, specific symptoms and progression of these disorders vary greatly. Duchenne and Becker muscular dystrophies are two other types of muscular dystrophies that are usually classified separately. (For more information on these disorders, choose the specific disease name as your search term in the Rare Disease Database.)

Diagnosis

The evaluation of a patient with suspected SMA, such as an infant with unexplained weakness and hypotonia while appearing bright eyed and socially engaging, begins with a complete patient history and physical examination. If the clinical evaluation shows signs of lower motor neuron disease (see Signs & Symptoms section) and suggests SMA, the diagnosis is confirmed with genetic testing to detect pathogenic variants in the SMN1 gene and if there are no copies of SMN1, then reflex testing for SMN2 copy number should be competed. If the patient is symptomatic and one copy of SMN1 is identified, then gene sequence analysis should be obtained to evaluate for a possible SMN1 point mutation.

No other tests are needed to diagnose SMA, although additional testing may be initially performed to exclude other conditions that could have a similar clinical presentation. This can include genetic testing associated with other diseases, metabolic or biochemical tests or evaluation of the transmission of electrical signals from nerves to muscles (electromyography; EMG). Muscle biopsy may be considered when the above testing does not reveal a diagnosis.

Newborn screening for SMA is being implemented throughout the United States. As of January 2021, 39 states screen for SMA representing 86% of all infants born in the U.S. Newborn screening facilitates early identification of infants with SMA and thus early implementation of treatment. Infants identified by SMA newborn screening are urgently referred for confirmatory testing, discussion of treatments and care. Early treatment prior to the onset of symptoms provides the best outcomes. Newborn screening will not identify 3-5% of infants with SMA due to having a point mutation in the SMN1 gene. These infants will progress to develop symptoms and require rapid diagnosis and treatment.

Carrier testing for SMA is also available using a molecular genetic test in which the number of copies of the SMN1 gene is determined. The American College of Obstetricians and Gynecologists recommends offering carrier screening for SMA to all women who are considering pregnancy or are currently pregnant.

Standard Therapies

The treatment of SMA requires a multidisciplinary team approach and should notably include neurologists, medical geneticists, physical therapists, speech pathologists, pulmonologists, respiratory therapists, medical social workers, nutritionists, psychologists and specialized nurses. There are two main components to SMA management: treatment that slows the progression of the disease (disease-modifying therapy) and therapy that helps manage symptoms and improves quality of life (supportive therapy). Genetic counseling is recommended for affected individuals and their families.

Symptomatic therapy

The symptomatic management of SMA includes physical therapy, occupational therapy, monitoring respiratory function and intervening as clinically indicated, nutritional status monitoring and intervention, spine curvature monitoring and intervention and use of orthotics and adaptive equipment as needed. Respiratory support for SMA type 1 (infants symptomatic prior to 6 months of age) includes providing breathing support called BiPAP (bi-level positive airway pressure) to manage hypoventilation and a mechanical insufflation-exsufflation device to support weak cough. Supportive management has been shown to increase comfort and life expectancy. Earlier in the disease, some affected infants might only require ventilation support at night. Children with progressive respiratory insufficiency might require more invasive interventions to breathe, such as surgical placement of a breathing tube through the neck (tracheostomy). For infants and children with dysphagia, nutrition support may require gastrostomy tube placement to provide nutrition safely. Children with SMA may also require surgical intervention for musculoskeletal issues such as scoliosis and/or hip dislocation.

Disease-modifying therapy

Research efforts have led to therapies that can improve the course of SMA. The first disease-modifying therapy was approved by the U.S. Food and Drug Administration (FDA) in 2016. These therapies have shown promising results, notably developmental motor milestone achievement and improved survival in treated individuals. As the impact of these treatments are being studied, keep in mind that these treatments are not cures.

In 2016, nusinersen (Spinraza) was approved by the FDA as the first drug to treat children and adults with SMA. Nusinersen is an injection administered into the fluid surrounding the spinal cord (intrathecal administration). Nusinersen acts by modifying the splicing of the SMN2 gene product, mRNA, so that more full length and functional SMN protein is produced.

In 2019, the FDA approved onasemnogene abeparvovec-xioi (Zolgensma) for the treatment of children less than two years of age with SMA. Onasemnogene abeparvovec-xioi is a gene therapy that delivers a fully functional copy of human SMN1 gene into the target motor neuron cells via a viral vector, AAV9. A one-time intravenous administration of the medication results in increased SMN protein in all cells including motor neurons.

In 2020, the FDA approved risdiplam (Evrysdi) to treat patients two months of age and older with SMA. Risdiplam is the first orally administered drug approved for the treatment of SMA. It has a mechanism of action is also to modify splicing of the SMN2 mRNA resulting in increased SMN protein.

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Investigational Therapies

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 NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [emailprotected]

Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/

For information about clinical trials sponsored by private sources, contact: www.centerwatch.com

For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

NORD Member Organizations

  • Child Neurology Foundation
  • Cure SMA
    • 925 Busse Road
    • Elk Grove Village, IL 60007
    • Phone: (847) 367-7620
    • Toll-free: (800) 886-1762
    • Email: [emailprotected]
    • Website: http://www.cureSMA.org/
  • Muscular Dystrophy Association
    • 161 N. Clark
    • Suite 3550
    • Chicago, IL 60601 USA
    • Phone: (520) 529-2000
    • Toll-free: (800) 572-1717
    • Email: [emailprotected]
    • Website: http://www.mda.org/

Other Organizations

  • Children with Spinal Muscular Atrophy, Ukraine – Kharkiv Charitable Foundation
    • Gogolia Street 7
    • Kharkiv, 61057 Ukraine
    • Phone: 380503640673
    • Email: [emailprotected]
    • Website: http://www.csma.org.ua
  • Genetic and Rare Diseases (GARD) Information Center
  • New Horizons Un-Limited, Inc.
    • 811 East Wisconsin Ave
    • P.O. Box 510034
    • Milwaukee, WI 53203 USA
    • Phone: (414) 299-0124
    • Email: [emailprotected]
    • Website: http://www.new-horizons.org
  • NIH/National Institute of Neurological Disorders and Stroke
  • Spinal Muscular Atrophy Foundation
    • 888 Seventh Avenue
    • Suite 400
    • New York, NY 10019 USA
    • Phone: (646) 253-7100
    • Toll-free: (877) 386-3762
    • Email: inf[emailprotected]
    • Website: http://www.smafoundation.org
  • Spinal Muscular Atrophy Support UK
    • 40 Cygnet Court
    • Timothy's Bridge Road
    • Warwickshire, CV37 9NW United Kingdom
    • Phone: 4401789267520
    • Email: [emailprotected]
    • Website: http://www.smasupportuk.org.uk/

References

TEXTBOOKS

Russman BS. Spinal Muscular Atrophy. In: The NORD Guide to Rare Disorders, Philadelphia,PA: Lippincott, Williams and Wilkins, 2003:637.

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JOURNAL ARTICLES

Baranello G, Darras BT, Day JW, et al. Risdiplam in type 1 spinal muscular atrophy. N Engl J Med. Mar 11 2021;384(10):915-923. doi:10.1056/NEJMoa2009965

Darras BT, Masson R, Mazurkiewicz-Beldzinska M, et al. Risdiplam-treated infants with type 1 spinal muscular atrophy versus historical controls. N Engl J Med. Jul 29 2021;385(5):427-435. doi:10.1056/NEJMoa2102047

Day JW, Finkel RS, Chiriboga CA, et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. Apr 2021;20(4):284-293. doi:10.1016/S1474-4422(21)00001-6

Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: final report of a phase 2, open-label, multicentre, dose-escalation study. Lancet Child Adolesc Health. 2021;5:491-500.

Glascock J, Sampson J, Connolly AM, et al. Revised recommendations for the treatment of infants diagnosed with spinal muscular atrophy via newborn screening who have 4 copies of SMN2. J Neuromuscul Dis. 2020;7(2):97-100. doi:10.3233/JND-190468

Hagenacker T, Wurster CD, Gunther R, et al. Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurol. Apr 2020;19(4):317-325. doi:10.1016/S1474-4422(20)30037-5

Maggi L, Bello L, Bonanno S, et al. Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3. J Neurol Neurosurg Psychiatry. Nov 2020;91(11):1166-1174. doi:10.1136/jnnp-2020-323822

Stevens D, Claborn MK, Gildon BL, Kessler TL, Walker C. Onasemnogene Abeparvovec-xioi: gene therapy for spinal muscular atrophy. Ann Pharmacother. 2020;54:1001-9.

De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. Nov 2019;29(11):842-856. doi:10.1016/j.nmd.2019.09.007

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. Mar 2018;28(3):197-207. doi:10.1016/j.nmd.2017.11.004

Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378:625-35.

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. Feb 2018;28(2):103-115. doi:10.1016/j.nmd.2017.11.005

Ratni H, Ebeling M, Baird J, et al. Discovery of Risdiplam, a selective survival of motor neuron-2 (SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA). J Med Chem. 2018;61:6501-17.

Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377:1723-32.

Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377:1713-22.

Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet J Rare Dis. 2017;12:124.

Sugarman EA, Nagan N, Zhu H, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012;20(1):27-32. doi:10.1038/ejhg.2011.134

D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis 2011;6:71.

Wu JS, Darras BT, Rutkove SB. Assessing spinal muscular atrophy with quantitative ultrasound. Neurology. 2010;75(6):526-31.

Rutkove SB, Shefner JM, Gregas M, et al. Characterizing spinal muscular atrophy with electrical impedance myography. Muscle Nerve. 2010;42(6):915-21.

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Lewelt A, Krosschell KJ, Scott C, et al. Compound muscle action potential and motor function in children with spinal muscular atrophy. Muscle Nerve. 2010;42(5):703-8.

Renbaum P, Kellerman E, Jaron R, et al. Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. Am J Hum Genet. 2009;85(2):281-9..

Kaufmann P, Muntoni F; International Coordinating Committee for SMA Subcommittee on SMA Clinical Trial Design. Issues in SMA clinical trial design. The International Coordinating Committee (ICC) for SMA Subcommittee on SMA Clinical Trial Design. Neuromuscul Disord. 2007;17(6):499-505.

Swoboda KJ, Prior TW, Scott CB, et al. Natural history of denervation in SMA: relation to age, SMN2 copy number, and function.Ann Neurol. 2005;57(5):704-12.

Mellies U, Dohna-Schwake C, Stehling F, Voit T. Sleep disordered breathing in spinal muscular atrophy. Neuromuscul Disord. 2004;14(12):797-803.

Sporer SM, Smith BG. Hip dislocation in patients with spinal muscular atrophy. J Pediatr Orthop. 2003;23(1):10-4.

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 spina

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.

Bach JR, Baird JS, Plosky D, Navado J, Weaver B. Spinal muscular atrophy type 1: management and outcomes. Pediatr Pulmonol. 2002;34(1):16-22.

INTERNET

Bodamer OA. Spinal Muscular Atrophy. UpToDate. Last updated: Dec 22, 2021. https://www.uptodate.com/contents/spinal-muscular-atrophy Accessed Jan 11, 2022.

Prior TW, Leach ME, Finanger E. Spinal Muscular Atrophy. 2000 Feb 24 [Updated 2020 Dec 3]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1352/ Accessed Jan 11, 2022.

The American College of Obstetricians and Gynecologists: Carrier Screening for Genetic Conditions. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/03/carrier-screening-for-genetic-conditions. Accessed January 11, 2022.

Years Published

2004, 2005, 2006, 2007, 2008, 2012, 2022

The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.

The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.

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FAQs

What does it mean to be a carrier of SMN1? ›

A carrier is a person who inherits one healthy copy and one faulty copy of the SMN1 gene. About 1 in 40 to 1 in 60 people are carriers of SMA. If both parents are carriers, they have a 1-in-4 chance of having a child with SMA. About 1 in 6,000 to 1 in 10,000 children are born with SMA.

How many copies of SMN1 should you have? ›

Typically, people have two copies of the SMN1 gene and one to two copies of the SMN2 gene in each cell. However, the number of copies of the SMN2 gene varies, with some people having up to eight copies.

What does negative for SMN1 deletion mean? ›

Negative result

A negative test result is characterized by the presence of detectable amounts of SMN1 exon 7, with an SMN1 exon 7 copy number of >1, with the presence of subtle intragenic point mutations within the SMN1 gene having been ruled out.

How common is SMN1 gene? ›

Roughly 1 in 50 (or approximately 6 million) people in the United States carries a copy of the mutated SMN1 gene responsible for SMA. These people are called carriers.

Does everyone have SMN1 gene? ›

Most people have two functioning copies of the SMN1 gene. People with one non-working copy and one working copy of the gene are called “carriers.” Carriers generally do not show signs and symptoms of spinal muscular atrophy (SMA) but could be at risk to have a child affected with the condition.

Do both parents have to be carriers for spinal muscular atrophy? ›

Both parents must be carriers for the baby to be at risk for SMA. If your partner has a negative test result and no family history of SMA, the chance that your baby will have SMA is less than 1%.

What is the difference between SMN1 and SMN2? ›

The SMN1 and SMN2 genes are more than 99 percent identical and lie within an inverted duplication on chromosome 5q13. 2 [5]. SMN1 lies telomeric of SMN2. The main difference between them is a C to T transition in exon 7 of SMN2 [9,10].

Where is the SMN1 gene located? ›

The SMN1 and SMN2 (601627) genes lie within the telomeric and centromeric halves, respectively, of a large, inverted duplication on chromosome 5q13.

Is 3 copies of SMN1 normal? ›

Second, the copy number of SMN1 can vary on a chromosome; we have observed that approximately 5% of the normal population possess three copies of SMN1. It is therefore possible for a carrier to possess one chromosome with two copies and a second chromosome with zero copies.

What are the symptoms of spinal muscular atrophy? ›

What are the symptoms of spinal muscular atrophy?
  • muscle weakness and decreased muscle tone.
  • limited mobility.
  • breathing problems.
  • problems eating and swallowing.
  • delayed gross motor skills.
  • spontaneous tongue movements.
  • scoliosis (curvature of the spine)

Can SMA be cured completely? ›

It's not currently possible to cure spinal muscular atrophy (SMA), but research is ongoing to find new treatments. Treatment and support is available to manage the symptoms and help people with the condition have the best possible quality of life.

Can someone with SMA have a baby? ›

Couples of all ages can be SMA carriers and have a baby with SMA.

How long do people with SMA live? ›

Infants with type 1 SMA usually die before their second birthday. Children with type 2 or type 3 SMA may live full lives depending on the severity of symptoms. People who develop SMA during adulthood (type 4) often remain active and enjoy a normal life expectancy.

What is the life expectancy of a child with SMA type 2? ›

The current life expectancy for people living with SMA type 2 is around 25. However, research is in progress to determine how the newest therapies and treatments from current clinical trials will impact life span and quality of life.

Who is the oldest person with SMA? ›

They have the hearts and minds and courage to keep learning.” Steve Mikita is one of the oldest people living with SMA at 64 years old.

What does SMN1 gene do? ›

The SMN1 gene provides instructions for making the survival motor neuron (SMN) protein. The SMN protein is found throughout the body, with highest levels in the spinal cord.

What is SMN1 variant? ›

Spinal muscular atrophy (SMA) is a neurodegenerative disease of lower motor neurons, leading to progressive weakness associated with ventilatory insufficiency. The most common form of SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene located at 5q13.

What is the difference between SMN1 and SMN2? ›

The SMN1 and SMN2 genes are more than 99 percent identical and lie within an inverted duplication on chromosome 5q13. 2 [5]. SMN1 lies telomeric of SMN2. The main difference between them is a C to T transition in exon 7 of SMN2 [9,10].

What chromosome is SMN1 on? ›

The most common form of SMA (types 1-4) is caused by a defect (mutation) in the SMN1 gene on chromosome 5. (People have two SMN1 genes — one on each chromosome 5). In 94% of all SMA cases, this mutation involves a deletion in a segment known as exon 7.

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Name: Greg Kuvalis

Birthday: 1996-12-20

Address: 53157 Trantow Inlet, Townemouth, FL 92564-0267

Phone: +68218650356656

Job: IT Representative

Hobby: Knitting, Amateur radio, Skiing, Running, Mountain biking, Slacklining, Electronics

Introduction: My name is Greg Kuvalis, I am a witty, spotless, beautiful, charming, delightful, thankful, beautiful person who loves writing and wants to share my knowledge and understanding with you.