The age of onset determines the level of motor neuron degeneration.1,2 Cognitive ability does not appear to be impacted by spinal muscular atrophy.2
Clinical literature shows a wide range of the incidence and prevalence of spinal muscular atrophy:
The genetic deficit underlying spinal muscular atrophy is well characterised. The role of the survival motor neuron 1 (SMN1) gene is to produce SMN protein, which is highly expressed in the spinal cord and is known to be essential for motor neuron survival.1,6
In SMA, homozygous mutations or deletions of SMN1 produce a shortage of SMN protein, which causes degeneration of motor neurons in the spinal cord.7,8
Nearly all people, including those with SMA, have a second, virtually duplicate gene to SMN1, known as survival motor neuron 2 (SMN2).2,10
Approximately 10% of SMN2 transcripts result in full-length SMN protein, providing patients with an insufficient amount of SMN protein to sustain survival of spinal motor neurons in the CNS.2
Due to deficiency of the gene SMN1... 1,11
Partially compensated by the gene SMN2… 1,11
Copy number of SMN2 is variable in patients with spinal muscular atrophy, and higher copy numbers of SMN2 correlate with less-severe disease:2
of individuals with spinal muscular atrophy retain at least 1 copy of SMN2
The copy number of SMN2 correlates to disease phenotype.
1 or 2 COPIES
of individuals with Type I spinal muscular atrophy have 1 or 2 copies of SMN2
of individuals with Type II spinal muscular atrophy have 3 copies of SMN2
The higher the number of SMN2 gene the milder the disease type.
3 or 4 COPIES
of individuals with Type III spinal muscular atrophy have 3 or 4 copies of SMN2
SMN2 copy number is related to, but not predictive of, disease severity, and care decisions should not be made based on copy number alone 12,13
In any case of spinal muscular atrophy, SMN2 copy number is less predictive of prognosis than age of onset and functional abilities14,15
In addition to SMN2, there is some evidence of other genetic modifiers of disease severity, including levels of the protein Plastin-313
Because of its potential role in modulating disease severity, SMN2 is a target for therapeutic interventions.16
The characters shown are real patients and the required consent to use their stories has been obtained from the patients and families. Photographs are for illustrative purposes only.
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2. Darras BT, Royden Jones H Jr, Ryan MM, De Vivo DC, eds. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. 2nd ed. London, UK: Elsevier; 2015.
3. Lally C, et al. Indirect estimation of the prevalence of spinal muscular atrophy Type I, II, and III in the United States. Orphanet Journal of Rare Diseases 2007; 12(1): 175.
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8. Medline Plus. Genetics Home Reference. SMN1. [online] 2016 Apr 20 [cited 2020 Sept 30]. Available from: URL: https://ghr.nlm.nih.gov/gene/SMN1.
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12. TREAT-NMD A Guide to the 2017 International Standards of Care for SMA. Available from: URL: https://treat-nmd.org/wp-content/uploads/2019/06/uncategorized-A-Guide-to-the-2017-International-Standards-of-Care-for-SMA_UKEnglish_Digital-v2L.pdf.
13. 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.
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16. Monani UR. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron 2005;48(6):885-896.