Spinal muscular atrophy (SMA)
Spinal muscular atrophy (SMA)
Alternative names
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5q SMA types 1, 2, 3, 4
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About the condition
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SMA is a genetic disorder due to a bi-allelic (homozygous) deletion in the Survival Motor Neuron 1
(SMN1) gene located on chromosome 5q. It affects the motor neurons of the spinal cord and results in
progressive muscle weakness (atrophy) and an inability to control movement in the arms, legs, face,
chest, throat, and tongue, as well as skeletal muscle activity including speaking, walking, swallowing,
and breathing. In the most severe cases babies will not ever be able to sit, crawl or walk.
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Inheritance
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Autosomal recessive
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Year screening started in WA |
2023 |
Incidence in WA
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1:11,000 births
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Defect
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Homozygous deletion of exon 7 in SMN1 gene. The clinical severity is modified by the copy number of SMN2
genes. SMA Types 1-4 have increasing SMN2 copy numbers and decreasing clinical severity.
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Symptoms if untreated
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Babies present with hypotonia, floppiness and muscle weakness causing difficulty with motor milestones
like sitting, standing walking. With severe SMA there can be weak respiratory muscles, difficulty in
swallowing, failure to thrive. As the child grows there can be significant musculoskeletal issues such
as spinal curvature (scoliosis) and contractures.
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Determinants on
bloodspot screening
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SMN1 deletion analysis by PCR analysis
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Diagnostic tests
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SMN1 and SMN2 genotyping
Clinical (neuromuscular) assessment and genetic counselling
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Treatment
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There are three potential treatments depending on the age at the time of diagnosis:
- Onasemnogene
abeparvovec-xioi (Zolgensma) is a gene therapy, which replaces the SMN1 gene
- Nusinersen (Spinraza)
is an intrathecal treatment and increases SMN protein produced by the SMN2 gene; and
- Risdiplam
(Evrysdi) is an oral drug, which increases SMN protein produced by the SMN2 gene.
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Screening issues
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Newborn screening for SMA is directed to SMA caused by homozygous deletion of exon 7 in the SMN1
gene. Other forms of SMA that occur may not be detected by screening.
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Last reviewed: 25-01-2023