- Authors of report
- W. David Arnold, Darine Kassar, John T. Kissel
- Date of report
- Medical conditions
- Spinal muscular atrophy
- Introduction to SMA:
- SMA is a group of disorders associated with spinal motor neuron loss.
- The most common form of SMA is proximal or 5q SMA.
- Historically, diagnosis was based on electromyography and muscle biopsy features of denervation. Now, molecular testing for homozygous deletion or mutation of the SMN1 gene is used for diagnosis.
- Cause and Pathogenesis:
- Humans have two nearly identical SMN genes on chromosome 5q13.
- Homozygous deletion of the SMN1 gene was identified as the cause of SMA in 1995.
- SMN1 and SMN2 genes differ by only a few base pairs. A single nucleotide difference in SMN2 affects splicing, leading to ~90% of its transcripts lacking exon7.
- As a result, SMN2 produces a shortened, unstable protein, whereas SMN1 produces the full-length SMN protein.
- The combined effects of homozygous loss of SMN1 and retention of SMN2 result in low levels of the full-length SMN protein.
- Full-length SMN protein is essential for various cellular functions, including RNA metabolism.
- While SMN plays a key role in RNA splicing in all cells, its exact role in motor neurons is still under investigation.
- Variability of Clinical Features and Severity:
- The main clinical features of SMA are muscle weakness and atrophy due to motor neuron dysfunction and loss.
- The severity spectrum ranges from mild proximal limb weakness in adulthood to severe generalized weakness with respiratory failure in neonates.
- The onset and progression of weakness in SMA are distinct from many other motor neuron disorders. There’s usually a presymptomatic period, followed by rapid progression and then a relatively static phase.
- SMA has been traditionally classified into types 1–3, but some experts suggest more subtypes. The type and severity correlate with the SMN2 copy number.
- Clinical Features of Type 1 SMA:
- Type 1 SMA is the most common and severe form, representing 45% of cases.
- Infants may appear normal before developing symptoms like limb weakness, respiratory distress, weak cry, and poor feeding.
- Affected babies often have a “frog-leg” lower limb posture due to severe hypotonic weakness.
- Paradoxical breathing is a characteristic feature.
- Tongue fasciculations are common, but cognition is spared.
- By definition, these infants never achieve the ability to sit independently. Most cases have a natural history of death before age 2, but aggressive supportive care can improve survival.
This is a summary of independent research published elsewhere. It is not a report of Beike treatment outcomes.
