Spinal muscular atrophy

Cause of SMA

Due to a change in the SMN1 gene, there is a deficiency of the SMN protein. The SMN protein is important for the motor neurons in the spinal cord, which transmit information from the brain to the muscles. Over time, this deficiency leads to destruction of the motor neurons and atrophy of the muscles - resulting in muscle weakness.

In people with SMA, the formation of SMN protein is limited to the activity of the SMN2 gene. However, 90% of the SMN protein produced by the SMN2 gene is unstable and rapidly degrades (see figure 1). The copy number of the SMN2 gene varies from person to person. Therefore, the lower the SMN2 gene copy number, the more severe the disease.2,3

Figure 1: Role of SMN1 and SMN2 genes in SMA.³

Inheritance of SMA

SMA is an autosomal recessive inherited disease. This means that both parents must carry a defective SMN1 gene for their offspring to develop SMA. Thus, the probability of the offspring developing SMA is 25%. Studies have shown that about 1 in 50 people are carriers (see figure 2).3-4

Figure 2. Autosomal-recessive inheritance of SMA.⁴

Classification of spinal muscular atrophy into different types

Traditionally, SMA has been classified into three or four types, depending on the age of onset and the most advanced motor stage of development acquired by the individual (see figure 3). This classification does not provide any information about the actual current motor abilities of the affected person, nor about any associated limitations.

In approximately 60% of cases, it is SMA type I. The onset of SMA in adulthood (type IV) is much more rare than the other forms (not described in figure 3).5 In addition, there is another form of SMA (type 0) that begins in utero, is very severe and is usually fatal before the age of six months, sometimes already in utero. 6

Type I Werdnig-Hoffmann
Type III Kugelberg-Welander
Best function achieved
Never able to sit
Able to sit, never able to stand
Able to stand and walk
Age at disease onset
0-6 months
7-18 months
> 18 months
Typical clinical symptoms
Intense hypotonia and muscle weakness, weak crying and coughing, difficulty swallowing (even one's own saliva), early death from respiratory failure and aspiration pneumonia
Delayed motor development, fine hand tremor, weak cough, joint contractures and scoliosis
Muscle weakness of varying intensity, frequent muscle cramps, overuse of joints, loss of ability to walk as the disease progresses

Figure 3: Classification of SMA in 3 types (types 0 and IV are not described here) - this table describes the natural  evolution of the disease, without a disease-modifying treatment. 7-13

The therapeutic approach in the treatment of SMA is multidisciplinary

Spinal muscular atrophy is a complex disease and therefore requires integrated treatment by a multidisciplinary care team (see figure 4). Coordination should be provided by the neurologist or neuro pediatrician. The type of management depends on the severity of the disease and individual patient complications. Treatment of SMA takes place in specialized treatment centers.

What does the multidisciplinary management of SMA usually include?

  • A disease-modifying treatment for SMA

  • Symptomatic treatment of potential complications

  • Respiratory support

  • Physiotherapy/ergotherapy

  • Orthopedic care, support and aids

Figure 4. Multidisciplinary treatment approach to SMA; adapted from¹³

M-CH-00002604   07/2022


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

  2. Feldkotter M, et al. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet 2002; 70:358-368. Pubmed-Link

  3. Bowerman M, et al. Therapeutic strategies for spinal muscular atrophy: SMN and beyond. Dis Model Mech 2017; 10:943-954. Pubmed-Link

  4. Sugarman EA, 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; 20:27-32. Pubmed-Link

  5. Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurol Clin 2015; 33:831-846. Pubmed-Link

  6. Dubowitz V. Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. Eur J Paediatr Neurol 1999; 3:49-51. Pubmed-Link

  7. Finkel RS et al. (2017) ENMC SMA Workshop Study Group. 218th ENMC International Workshop: Revisiting the consensus on standards of care in SMA Naarden, The Netherlands, 19-21 February 2016. Neuromuscul Disord 27 (6):596-605.

  8. Butchbach ME. Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases. Front Mol Biosci 2016; 3:7. Pubmed-Link

  9. Prior TW. Perspectives and diagnostic considerations in spinal muscular atrophy. Genet Med 2010; 12:145-152. Pubmed-Link

  10. Crawford TO, et al. Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study. PLoS One 2012; 7:e33572. Pubmed-Link

  11. Farrar, M., Park, S., Vucic, S., Carey, K., Turner, B., Gillingwater, T., Swoboda, K. and Kiernan, M., 2017. Emerging therapies and challenges in spinal muscular atrophy. Annals of Neurology, 81(3), pp.355-368.

  12. MunsatTL,DaviesKE.InternationalSMAconsortiummeeting.(26-28June1992,Bonn, Germany). Neuromuscul Disord 1992; 2:423-428. Pubmed-Link

  13. Bladen CL, et al. Mapping the differences in care for 5,000 spinal muscular atrophy patients, a survey of 24 national registries in North America, Australasia and Europe. J Neurol 2014; 261:152-163. Pubmed-Link

  14. Kaufmann P, et al. Prospective cohort study of spinal muscular atrophy types 2 and 3. Neurology 2012; 79:1889-1897. Pubmed-Link

  15. MercuriE,etal.Diagnosisandmanagementofspinalmuscularatrophy:Part1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord 2018; 28:103-115. Pubmed-Link

Spinal muscular atrophy (SMA) is a rare, hereditary neuromuscular disease that leads to muscle weakness and, depending on its severity, impairment of other parts of the body. Worldwide, SMA affects approximately 1 in 10,000 newborns.¹ It is estimated that there are currently 130 patients with SMA in Switzerland.

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