The differential diagnosis of 5q SMA includes,
but is not limited to:1

Spinal cord disorders

  • Neoplasms (SMA Types I, II, III)
  • Other myelopathies (SMA Types I, II, III)

Other motor neuron diseases

  • Spinal muscular atrophy with respiratory distress (SMARD) (SMA Type I)
  • Juvenile muscular atrophy of distal upper extremity (Hirayama disease)
  • Fazio-Londe disease, Brown-Vialetto-van Laere syndrome
  • Other non-5q SMAs (SMA Types I, II, III)
  • Juvenile amyotrophic lateral sclerosis (SMA Types I, II, III)


  • Congenital hypomyelinating or axonal neuropathy (SMA Types I, II)
  • Hereditary motor and sensory neuropathies (SMA Types I, II, III)
  • Chronic inflammatory demyelinating polyneuropathy (SMA Types II, III)

Neuromuscular junction disorders

  • Botulism (SMA Type I)
  • Congenital myasthenic syndromes (SMA Types I, II, III)
  • Lambert-Eaton myasthenic syndrome (SMA Type III)
  • Autoimmune myasthenia gravis (SMA Types II, III)


  • Congenital myopathies (SMA Types I, II, III)
  • Congenital myotonic dystrophy (SMA Type I)
  • Congenital muscular dystrophies (SMA Types I, II)
  • Muscular dystrophies (SMA Type III)
  • Mitochondrial myopathies (SMA Types I, II, III)
  • Acid maltase/Pompe disease (SMA Types I, II, III)
  • Other metabolic myopathies (SMA Types I, II, III)
  • Inflammatory myopathies (SMA Type III)
  • Channelopathies (SMA Type III)

Other disorders

  • Chromosomal abnormalities (SMA Types I, II, III)
  • Prader-Willi syndrome
  • Central nervous system abnormalities (SMA Types I, II, III)
  • Hexosaminidase A deficiency (SMA Types III, IV)

Learn more about the identification of paediatric neuromuscular disorders at:

Hypotonia in infants

Infants with hypotonia (“floppy babies”) often pose a diagnostic challenge for clinicians because hypotonia may be the presenting sign of both benign and serious conditions. Classic signs may be displayed by hypotonic infants, including:

Facial weakness may be an important clinical sign for differentiating myopathies from muscular dystrophies and SMA.5

  • There is typically facial sparing in SMA5

Once the individual has been identified as hypotonic, it may be helpful to know if there is weakness in addition to a tone abnormality or if the individual is hypotonic but normally strong.4

Hypotonia with profound weakness may suggest a lower motor neuron disorder such as SMA.6

Time to diagnosis is critical – earlier diagnosis and intervention may help improve the outcomes for individuals with SMA.7

If you suspect SMA or a neuromuscular disorder in any of your patients, refer to paediatric neurologist for an urgent appointment.

  1. Darras BT et al. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. 2nd ed. London, UK: Elsevier; 2015. 
  2. Leyenaar J et al. Paediatr Child Health 2005; 10: 397–400.
  3. Peredo DE and Hannibal MC. Pediatr Rev 2009; 30: e66–e76. 
  4. Bodensteiner JB. Semin Pediatr Neurol 2008; 15: 10–20. 
  5. North KN. Semin Pediatr Neurol 2011; 18: 216–20. 
  6. Van Toorn R. CME: Your SA Journal of CPD 2004; 22: 449–55. 
  7. McDonald CM. Phys Med Rehabil Clin N Am 2012: 23: 495–563. 
  8. Rothwell E et al. Am J Med Genet A 2013; 161A: 679–86.