History of familial adult myoclonus epilepsy/benign adult familial myoclonic epilepsy around the world

Abstract

AbstractFamilial adult myoclonus epilepsy/benign adult familial myoclonic epilepsy (FAME/BAFME) has emerged as a specific and recognizable epilepsy syndrome with autosomal dominant inheritance found around the world. Here, we trace the history of this syndrome. Initially, it was likely conflated with other familial myoclonus epilepsies, especially the progressive myoclonus epilepsies. As the progressive myoclonus epilepsies became better understood clinically and genetically, this group began to stand out and was first recognized as such in Japan. Subsequently, families were recognized around the world and there was debate as to whether they represented one or multiple disorders. Clarification came with the identification of pentanucleotide repeats in Japanese families, and FAME/BAFME was quickly shown to be due to pentanucleotide expansions in at least six genes. These have geographic predilections and appear to have been caused by historically ancient initial mutations. Within and between families, there is some variation in the phenotype, explained in large part by expansion size, but whether there are features specific to individual genes remains uncertain.