Spinal muscular atrophy (SMA)

Alternative names	5q SMA types 1, 2, 3, 4
About the condition	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.
Inheritance	Autosomal recessive
Year screening started in WA	2023
Incidence in WA	1:11,000 births
Defect	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.
Symptoms if untreated	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.
Determinants on bloodspot screening	SMN1 deletion analysis by PCR analysis
Diagnostic tests	SMN1 and SMN2 genotyping Clinical (neuromuscular) assessment and genetic counselling
Treatment	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.
Screening issues	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.

Last reviewed: 25-01-2023