Genotypic and phenotypic heterogeneity in amyotrophic lateral sclerosis

Abstract

Genetic risk factors play a major role in the susceptibility to amyotrophic lateral sclerosis (ALS), the most common motor neuron disease of the adult. Although genetic studies have partially elucidated the genetic background of the disease, a large part of ALS heritability is still missing. In this chapter, we discuss the major genes implicated in the pathogenesis of motor neuron diseases; the clinical, pathological, and genetic links between ALS and frontotemporal dementia; and the vast genotypic and phenotypic heterogeneity of ALS. Lastly, we review the most recent strategies for identification of novel genetic risk factors in ALS, detailing their advantages and potential pitfalls.