Chapter 10 - Amyotrophic lateral sclerosis and other disorders of the lower motor neuron

Summary

This chapter reviews the epidemiology, clinical phenotype, and genetic basis of the heritable forms of amyotrophic lateral sclerosis (ALS) and other disorders of the lower motor neuron (LMN) including Kennedy's disease, the spinal muscular atrophies (SMA), and hereditary motor neuropathies (HMN). The first successful genome-wide linkage study on FALS described linkage to chromosome 21q21. Mutations were subsequently identified in the gene encoding Cu/Zn superoxide dismutase (SOD1). Many people with sporadic ALS seek genetic counseling once they become aware that ALS can be genetic and are better informed about gene testing. The implications of gene screening should always be discussed in detail with the family prior to testing. Consent and DNA from an affected individual should be obtained before predictive testing in at-risk individuals is considered. The penetrance of different SOD1 mutations in particular varies greatly and must be taken into consideration when ascribing risk to a particular gene carrier.