The genetics of motor neuron diseases

Motor neuron diseases may be divided into three categories: those with lower motor neuron involvement - spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA or Kennedy's disease); those with upper motor neuron involvement primary lateral sclerosis (PLS)(1,2) and the spastic paraplegias; and those with combined upper and lower motor neuron involvement - amyotrophic lateral sclerosis (ALS). Other familial motor neuron disorders include hereditary neuronopathies, GM2 gangliosidosis, and possibly the ALS/PD syndrome of Guam. The contribution of genetics to the etiopathogenesis of motor neuron disorder varies considerably, accounting for a high percentage of spinal muscular atrophies, but only a small fraction of cases of ALS. The mode of inheritance also varies, with examples of autosomal dominant (AD), autosomal recessive (AR), or X-linked kindreds. (Tables 1 and 2).