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The spinal muscular atrophies (SMAs) have been historically conceptualized as hereditary disorders preferentially affecting anterior horn cells and selected motor cranial nerve nuclei.1 As in all disorders caused or influenced by genetics, molecular biology has served to confound as much as clarify the nosology. We have become very aware that the historical boundaries of hereditary neuromuscular disease are inaccurate. Part of this confusion arises from phenotypic overlap. For example, although lower motor neuron (LMN) morbidity dominates most SMA phenotypes, upper motor neuron (UMN) features may occur in some forms of distal SMA. Conversely, hereditary spastic paraplegia is a predominantly UMN disorder but may have notable LMN features in some genotypes. Even more damaging to the historical nosology of hereditary neuromuscular disease is the discovery that mutations of a single gene may produce variable phenotypes that have been historically represented as two or more diseases (Table 8-1).


In this chapter, we will discuss the SMAs related to mutations of the survival motor neuron (SMN) gene, the non-SMN infantile forms of the disease, the rare childhood bulbar forms of motor neuron disease (MND), Hirayama disease, Kennedy disease, the distal SMAs, the scapuloperoneal forms of SMA, and the uncommon SMA phenotypes that occur in association with multisystem disorders (Tables 8-2 and 8-3).26 We emphasize this predominantly phenotypic classification as this remains, for the most part, the most practical means by which these disorders are recognized if not diagnosed.


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