ABSTRACT
This chapter deals with the four genes known to cause Mendelian inherited amyotrophic lateral sclerosis (ALS). The poor recording of FALS has made it difficult to delineate any possible clinical differences between FALS and sporadic ALS (SALS). Rare cases with frontotemporal dementia and ALS have been reported in pedigrees where other affected cases have been without obvious cognitive dysfunction. It is of importance to observe the variable age of onset of symptoms among members of the same family; an intrafamilial variation of 15–25 years is a common finding. It has proved to be difficult to find the genes predisposing to ALS. The age-dependent onset in adults, short disease duration, genetic heterogeneity, incomplete disease penetrance, misdiagnosis, etc. have hampered the availability of large pedigrees with multiple affected members in multiple generations, from whom DNA is available for genetic linkage analysis.
