Congenital Spinal Muscular Atrophy, Autosomal Dominant (SMA-LED)

Autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) encompasses a group of disorders characterized by lower motor neuron deficits and non-length dependent muscle weakness predominantly affecting lower limbs. SMA-LED belong to a wider group of conditions that together constitute the so-called hereditary motor neuronopathies. The phenotypic and genotypic spectrum of these disorders is ever expanding and while the distinguishing clinical presentation of SMA-LED (i.e., discrepancy between lower and upper limb involvement) is strongly suggestive for the diagnosis, upper limbs involvement, central nervous system manifestations or other complications can be present or develop with time. In this chapter we will give a general overview of motor neuronopathies and then focus on those conditions associated with a SMA-LED phenotype, including recently identified genes.