Spinal muscular atrophy is an autosomal recessive genetic disease in which a child inherits 2 deleted or mutated SMN1 genes—1 from each parent4:
The American College of Medical Genetics and Genomics (ACMG) recommends that because SMA is found in all populations, carrier screening should be offered to couples of all races and ethnicities. The ACMG suggests that the testing be performed either before conception or early in pregnancy to allow carriers to make informed reproductive choices.5
Molecular genetic testing is an important tool in the diagnosis of spinal muscular atrophy6,7
The SMN gene deletion test is recommended as the first diagnostic step for a patient suspected to have spinal muscular atrophy.
If a patient is found to have a single copy of the SMN1 gene and the clinical presentation is suggestive of SMA, sequencing of the remaining SMN1 gene may identify the mutation and confirm the diagnosis.7
Differential diagnoses of spinal muscular atrophy
Spinal muscular atrophy results from homozygous deletions or mutations involving the SMN gene at locus 5q13 of chromosome 5. There are many rare neuromuscular disorders (e.g., Lambert-Eaton myasthenic syndrome affects 0.05/100,000 people a year). These disorders may involve mutations in a variety of different genes that are not associated with 5q13. The differential diagnosis of 5q spinal muscular atrophy includes, but is not limited to9: |
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Spinal cord disorders
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Other motor neuron diseases
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Neuropathies
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Neuromuscular junction disorders
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Myopathies
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Other disorders
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References
1. Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155-165. 2. Kolb SJ, Kissel JT. Spinal muscular atrophy. Arch Neurol. 2011;68(8):979-984. 3. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371(9630):2120-2133. 4. National Organization for Rare Diseases. Spinal muscular atrophy. http://rarediseases.org/rarediseases/spinal-muscular-atrophy/. Updated 2012. Accessed April 17, 2016. 5. Prior TW; Professional Practice Guidelines Committee. Carrier screening for spinal muscular atrophy. Genet Med. 2008;10(11):840-842. 6. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis. 2011;6:71. 7. Wang CH, Finkel RS, Bertini ES, et al; and Participants of the International Conference on SMA Standard of Care. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049. 8. Rothwell E, Anderson RA, Swoboda KJ, Stark L, Botkin JR. Public attitudes regarding a pilot study of newborn screening for spinal muscular atrophy. Am J Med Genet A. 2013;161A(4):679-686. 9. 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.
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