Laura Peeters

14 | Chapter 1 Spinal muscular atrophy SMA is a recessive neuromuscular disorder with an incidence of approximately 1 in 10000 [22]. SMA is characterized by muscle weakness (proximal more than distal, Figure 2b) and atrophy, caused by a low level of full-length, stable survival motor neuron 1 (SMN1) protein resulting in progressive degeneration of motor neurons in the spinal cord [23]. SMN2 protein copy number is the most important biomarker for disease severity; a higher copy number is related to less disease severity [23, 24]. Patients are categorized based on disease onset and maximum acquired milestones (e.g. achieving independent sitting or walking) [8]. Type 1 (infantile onset) is the most severe type and results in a median survival of less than 2 years. Children with SMA type 2 (onset at 7-18 months of age) will be able to sit independently, but they will never stand or walk independently. Children with SMA type 3 (onset from 18 months to adulthood) can achieve independent standing and walking, although many patients lose these abilities later on with disease progression. In SMA type 4 disease onset is during adulthood. However, the entire clinical spectrum is represented more by a gradual spectrum of functional capacities rather than by distinct subtypes [26]. The natural course is now changing due to effective treatment with Spinraza® (nusinersen) [27]. This drug is reimbursed by the Dutch government since the summer of 2018 for Figure 2 Characteristic muscle involvement patterns in patients with DMD (A) and SMA (B) (adapted from [25])