Abstract
The progressive myoclonic epilepsies (PMEs) represent a rare but devastating group of syndromes characterized by epileptic myoclonus, typically action-induced seizures, neurological regression, medically refractory epilepsy, and a variety of other signs and symptoms depending on the specific syndrome. Most of the PMEs begin in children who are developing as expected, with the onset of the disorder heralded by myoclonic and other seizure types. The conditions are considerably heterogenous, but medical intractability to epilepsy, particularly myoclonic seizures, is a core feature. With the increasing use of molecular genetic techniques, mutations and their abnormal protein products are being delineated, providing a basis for disease-based therapy. However, genetic and enzyme replacement or substrate removal are in the nascent stage, and the primary therapy is through antiepileptic drugs. Epilepsy in children with progressive myoclonic seizures is notoriously difficult to treat. The disorder is rare, so few double-blinded, placebo-controlled trials have been conducted in PME, and drugs are chosen based on small open-label trials or extrapolation of data from drug trials of other syndromes with myoclonic seizures. This review discusses the major PME syndromes and their neurogenetic basis, pathophysiological underpinning, electroencephalographic features, and currently available treatments.