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

Although newborn screening is not yet standard practice, time to diagnosis is critical. Based on the natural history of the disease, earlier diagnosis leading to earlier interventions may help improve outcomes for children with SMA.8

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:

Spinal cord disorders
  • Neoplasms (SMA Types I, II, III)
  • Other myelopathies
Other motor neuron diseases
  • Spinal muscular atrophy with respiratory distress (SMARD)
  • Juvenile muscular atrophy of distal upper extremity (Hirayama disease)
  • Fazio-Londe disease, Brown-Vialetto-van Laere syndrome
  • Other non-5q SMAs
  • Juvenile amyotrophic lateral sclerosis
  • Congenital hypomyelinating or axonal neuropathy
  • Hereditary motor and sensory neuropathies
  • Chronic inflammatory demyelinating polyneuropathy
Neuromuscular junction disorders
  • Botulism
  • Congenital myasthenic syndromes
  • Lambert-Eaton myasthenic syndrome
  • Autoimmune myasthenia gravis
  • Congenital myopathies
  • Congenital myotonic dystrophy
  • Congenital muscular dystrophies
  • Muscular dystrophies
  • Mitochondrial myopathies
  • Acid maltase/Pompe disease
  • Other metabolic myopathies
  • Inflammatory myopathies
  • Channelopathies
Other disorders
  • Chromosomal abnormalities
  • Prader-Willi syndrome
  • Central nervous system abnormalities

How does the diagnostic process differ from the perspective of a parent/caregiver?

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