Spinal Muscular Atrophy (SMA) type 1, formerly known as Werdnig-Hoffmann disease, is the most common form of SMA, accounting for more than half of all reported cases.1 The onset of symptoms in type 1 SMA occurs after birth (differentiating it from type 0 SMA) and though patients may initially appear healthy, evidence of weakness is invariably present by 6 months of age.2
Patients with type 1 SMA will progress to have global hypotonia, symmetric weakness or paralysis, and often lack tone in the neck and thus have poor head control.1-3 The low tone and weakness associated with type 1 SMA may be worse in the lower extremities initially and may manifest as infants assuming a “frog leg posture” while lying flat on their backs.4 A mismatch between the more rapid progression of weakness in the intercostal muscles and the diaphragm can yield a “bell-shaped” chest and the observation of so-called “belly” or paradoxical breathing when accessory muscles compensate for the relative weakness of the intercostal musculature.3,4 The neurological examination of infants with type 1 SMA reveals reduced spontaneous movement, low or absent tone, weakness with inability to produce antigravity muscle response, marked reduction or absence of tendon reflexes with intact sensation. Tongue fasciculations may be present later in the disease. Electromyography in patients with type 1 disease will show abnormal spontaneous activity, and changes consistent with active denervation occurring alongside reinnervation.
While some infants with type 1 SMA may achieve some motor milestones, SMA causes progressive weakness, and a hallmark finding is a failure to achieve the ability to sit upright without assistance.3,5 Infants whose symptom onset occurs more than two months after birth appear to achieve the most developmental progress.2 Since there is relative sparing of the muscles served by the cranial nerves, infants with SMA type 1 may track visual stimuli, attend to faces, or smile until progression of the disease eradicates even these abilities.4 There is evidence that type 1 SMA does not cause encephalopathy and that intelligence is preserved.1
Mortality in type 1 SMA occurs when bulbar neurodegeneration impairs feeding and impairs the individual’s airway protection. A more proactive approach to SMA care including routine placement of gastrostomy tubes and early intervention for airway support appears to have prolonged patient lifespan beyond the first year of life with the median survival in one large case series estimated to be 13.6 months.4,6-8 Despite improved longevity, the most common cause of death in type 1 SMA remains aspiration pneumonia.2,4,6,7,9
References
1. Tizzano EF, Finkel RS. Spinal muscular atrophy: A changing phenotype beyond the clinical trials. Neuromuscular disorders : NMD. 2017;27(10):883-889.
2. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet journal of rare diseases. 2011;6:71.
3. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015;51(2):157-167.
4. Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurologic clinics. 2015;33(4):831-846.
5. De Sanctis R, Coratti G, Pasternak A, et al. Developmental milestones in type I spinal muscular atrophy. Neuromuscular disorders : NMD. 2016;26(11):754-759.
6. Gregoretti C, Ottonello G, Chiarini Testa MB, et al. Survival of patients with spinal muscular atrophy type 1. Pediatrics. 2013;131(5):e1509-1514.
7. Oskoui M, Levy G, Garland CJ, et al. The changing natural history of spinal muscular atrophy type 1. Neurology. 2007;69(20):1931-1936.
8. Belter L, Cook SF, Crawford TO, et al. An overview of the Cure SMA membership database: Highlights of key demographic and clinical characteristics of SMA members. J Neuromuscul Dis. 2018;5(2):167-176.
9. Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83(9):810-817.