Spinal muscular atrophy (SMA)

Spinal muscular atrophy (SMA) is one of the most common single gene neurodegenerative diseases with an estimated incidence of 1:6000 to 1:10,000 in newborns. Approximately 95% of cases are caused by a deletion in the SMN1 gene (survival of motor neuron 1) on the long arm of chromosome 5 that leads to a loss of functional production of the SMN protein. Molecular genetic testing that demonstrates the absence of both full SMN1 copies provides the diagnosis of SMA. Since this textbook was last written, gene-targeted medical drug therapies for SMA have been approved by the US Food and Drug Administration (FDA). These drug treatments have altered the historical clinical trajectories of the disease process and the way in which the disease is classified and treated. The first drug approved by the FDA (December 2016) for SMA treatment was Nusinersen (Spinraza). This drug increases the proportion of SMN2-mRNA that then produces a more full-length functional SMN2 protein and requires intrathecal administration. Another drug, Zolgensma, was approved by the FDA in May 2019 for SMA patients <2 years of age. This drug directly targets the dysfunctional SMN1 gene, instead of trying to increase production of the SMN2 protein. Zolgensma uses an adenovirus vector to deliver an intact copy of SMN1 via intravenous administration. Scoliosis is very prevalent in the SMA patient population with an incidence of 60-90% in children with SMA types 1 and 2. In a recent study, the lifetime probability of receiving spinal surgery was 80% in SMA types 1 and 2. In skeletally immature patients younger than 8-10 years of age, "growth friendly" spinal instrumentation that stabilizes and improves the spinal deformity, but allows for continued spinal growth and lung development is the treatment of choice. Patients greater than 10 years of age can usually be treated with definitive posterior spinal fusion and segmental instrumentation with or without extension to the pelvis, depending on the severity of the pelvic obliquity and ambulatory ability. A multidisciplinary approach is the key element in the perioperative management of SMA patients to help avoid complications.