To understand the role of SMN in disease it is therefore important to understand 1) the unique vulnerability of motor neurons to the deficiency of this ‘housekeeping gene’ 2) why a monogenic deficiency causes a wide spectrum of phenotypic severity and 3) whether defects in SMA are determined early in development or related to degeneration later in life [15]. This evidence concerns the gene SMN1 and proximal spinal muscular atrophy.