Vascular Perfusion Abnormalities in Infants with Spinal Muscular Atrophy

Abstract

Spinal muscular atrophy (SMA) is an important cause of death in children and SMA type I, also known as Werdnig-Hoffman disease, is the most severe form of this disease. We report 2 cases of infants with SMA I in whom a distal necrosis developed, a feature not previously reported. Poor perfusion, autonomic dysfunction, and position-dependent factors may all play a role in the development of this complication.

A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe Spinal Muscular Atrophy Transgenic Mice

“…Nevertheless, systemic delivery of VMO25 in newborn mild SMA mice showed striking success in rescuing tail and ear necrosis. Tail and ear necrosis is a typical feature in SMA mice with a mild phenotype (Hsieh-Li et al, 2000;Tsai et al, 2006), which could be reminiscent of the digit necrosis observed in some severe cases of type I SMA in children (Araujo et al, 2009;Rudnik-Schoneborn et al, 2010). Although the mechanism of tail necrosis in SMA mice is still unclear, a possibility is that it could be related to vasculopathy induced by skeletal muscle denervation or autonomic nervous system dysfunction (Tsai et al, 2006;Araujo et al, 2009;Hua et al, 2010;Rudnik-Schoneborn et al, 2010).…”

Motor neuron cell-nonautonomous rescue of spinal muscular atrophy phenotypes in mild and severe transgenic mouse models

“…The overt phenotype of these mouse models is distal tissue necrosis, particularly in the tail and ear pinnae, due to compromised vascular perfusion and subsequent thrombosis (Tsai et al 2006;Narver et al 2008), which has not been documented in patients with types II-IV SMA. However, vasculopathy has been occasionally observed in type I patients when their survival was significantly extended due to improvements in palliative care (Araujo et al 2009;Rudnik-Schoneborn et al 2010). Similarly, necrosis in the tail, ear pinnae, feet, legs, anus, etc.…”

“…Distal necrosis is a phenotypic feature in both mild and severe SMA mouse models (Hsieh-Li et al 2000;Tsai et al 2006;Narver et al 2008); digital necrosis has also been observed, albeit infrequently, in infants with severe SMA (Araujo et al 2009;Rudnik-Schoneborn et al 2010). Furthermore, cardiac failure is a common phenotypic trait in severe mouse models and has also been reported in some severe SMA patients (Rudnik-Schoneborn et al 2008;Bevan et al 2010;Heier et al 2010;Shababi et al 2010).…”

Antisense oligonucleotides and spinal muscular atrophy: skipping along: Figure 1.

“…These mice die, on average, at 11 d, and are very similar to SMND7 mice showing a clear motor neuron phenotype (Le et al 2005). In type 1 SMA patients, there have been reports of cases with distal necrosis associated with anomalous vascular perfusion, and thus it can be viewed that the mouse phenotype has some similarity to what is observed in humans (Araujo Ade et al 2009). However, this phenotype has not been reported in milder SMA cases, and the exact origins of this phenotype remain unclear, although in mice it is clearly dependent on SMN levels (i.e., eightcopy SMN2 mice do not show this phenotype) (Monani et al 2000).…”