C9orf72 and amyotrophic lateral sclerosis: The heritability of ALS risk was established with discovery of so-called familial forms of ALS, whereby transmission of risk often follows a recognizable form of Mendelian inheritance arising from highly penetrant variation in genes such as C9orf72, SOD1, TARDBP and FUS.2 However, the majority of ALS cases do not exhibit this strong familial clustering and instead are often defined as sporadic.