Spinal Muscular Atrophy Type 4

Spinal Muscular Atrophy Type 4

Spinal Muscular Atrophy (SMA) type 4 is the most recently classified form of SMA and has the latest age of onset of all the SMA disease types.1 SMA type 4 is the rarest form of SMA accounting for less than 1% of all identified cases.1,2 Patients with SMA type 4 will experience onset of weakness beginning in their fourth decade of life, but onset can occur at any time after age 18 years.1,3

The patient with SMA type 4 will present with mild weakness and increased fatiguability of proximal limb muscles.1 Gait disturbance if present will be relatively mild compared to other childhood onset forms of SMA.4 The triceps, deltoid, iliopsoas, and quadriceps muscles will usually be the weakest muscles in affected patients.5 Weakness will be progressive but will not evolve to include muscles involved in ventilation or eating.5

As with other forms of SMA, patients will not have neurocognitive deficits and sensory function will be normal.6 Electromyography will not feature fibrillations or the most overt denervation findings seen un other types of SMA but will demonstrate findings suggesting reinnervation in affected muscles.7

Patients with type 4 SMA have the mildest phenotypic presentation of SMA; mortality in this population has not been reported.4

References

1. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet journal of rare diseases. 2011;6:71.

2. Wadman RI, Wijngaarde CA, Stam M, et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4. European journal of neurology. 2018;25(3):512-518.

3. Lin CW, Kalb SJ, Yeh WS. Delay in Diagnosis of Spinal Muscular Atrophy: A Systematic Literature Review. Pediatr Neurol. 2015;53(4):293-300.

4. Tizzano EF, Finkel RS. Spinal muscular atrophy: A changing phenotype beyond the clinical trials. Neuromuscular disorders : NMD. 2017;27(10):883-889.

5. Juntas Morales R, Pageot N, Taieb G, Camu W. Adult-onset spinal muscular atrophy: An update. Revue neurologique. 2017;173(5):308-319.

6. Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurologic clinics. 2015;33(4):831-846.

7. Mishra VN, Kalita J, Kesari A, Mitta B, Shankar SK, Misra UK. A clinical and genetic study of spinal muscular atrophy. Electromyography and clinical neurophysiology. 2004;44(5):307-312.