Developmental Aspects and Pathological Findings in Spinal Muscular Atrophy

The neuropathology of spinal muscular atrophy (SMA) has been studied for over a century, yet as novel therapeutics transition to clinical trials in SMA patients, there is renewed interest in applying modern techniques to further characterize the timing and extent of cellular and tissue pathology. Several studies suggest SMA pathological alterations begin in utero disrupting normal development of the neuromuscular system. The chapter begins with a brief review of normal neuromuscular development. It then discusses the pathological abnormalities of the various components of the motor unit including the motor neuron soma, axon, neuromuscular junction synapse, and muscle highlighting described prenatal and postnatal changes in SMA patients.