Progressive myoclonic encephalopathies: From phenomenology to genes and proteins

Abstract

The progressive myoclonic epilepsies (PMEs) are a group of symptomatic generalized epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. Challenges with PME arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment. PMEs are characterized by myoclonic seizures, tonic–clonic seizures, and progressive neurological deterioration, typically with cerebellar signs and dementia; other signs however can be present especially during the progression of disease. Recent advances in molecular genetics have helped to achieve better understanding of the different disorders that cause PME. There are different forms of PME that have been more accurately defined with recent advances in genetic studies. In particular, especially in adult age, the most recognized forms included Unverricht–Lundborg disease (related to CSTB gene mutation formerly indicated as EPM1A), Lafora disease (related to EPM2A and EPM2B mutation), myoclonic epilepsy with ragged red fibers (a mitochondrial disease often related to MTTK mutation), neuronal ceroidolipofuscinoses (CLN2, CLN3, CLN5, CLN6), sialidoses (that include different forms secondary to neuraminidase deficiency) and dentatorubral-pallidoluysian atrophy (related to an abnormal CAG repeat). The paper is aimed to review the PMEs with emphasis on updated genetics, diagnosis, and therapeutic options.