Chapter 1 - Spinal Muscular Atrophy: 125 Years Later and on the Verge of a Cure

Abstract

The spinal muscular atrophies (SMA) encompass a group of inherited neurodegenerative disorders characterized by muscle weakness and atrophy associated with loss of spinal and sometimes bulbar motor neurons. The most common form of proximal SMA is associated with homozygous deletions or mutations of the survival motor neuron 1, SMN1, gene on chromosome 5q13.2, and is the focus of this book. In the century following the first clinical description of SMA in 1891, the wide clinical spectrum was recognized with detailed clinical and pathological descriptions. Since mapping the gene in 1990, there has been exponential growth in our understanding of the disease mechanism, with creation of animal models, sensitive outcome measures, establishment of standard of care guidelines, and the opportunity of promising clinical trials for patients with SMA.