Progressive Myoclonus Epilepsies: Clinical and Genetic Aspects

Abstract

The progressive myoclonus epilepsies (PMEs) are a group of rare genetic disorders previously shrouded in nosological confusion. Recent advances have clarified the features of these disorders and provided a rational approach to diagnosis. The major causes of PME are now known to be Unverricht—Lundborg disease, myoclonus epilepsy ragged‐red fiber (MERRF) syndrome, Lafora disease, neuronal ceroid lipofuscinoses, and sialidoses. Over the past 3 years, a series of molecular genetic findings have further refined the understanding of the PMEs. The specific mutation responsible for many cases of MERRF has been identified, and the genes for Unverricht—Lundborg disease and for juvenile neuronal ceroid lipofuscinosis have been linked to chromosomes 21 and 16, respectively. Although the PMEs are among the rarest of the inherited epilepsies, because of molecular genetic discoveries they may soon be the best understood at the neurobiologic level.

Progressive myoclonic epilepsies: review of clinical, molecular and therapeutic aspects

“…The jerks are usually severe, irregular, asynchronous and predominate in the morning upon awakening, occurring in any segment of the body [1][2][3]9]. The tonic clonic seizures are very common and absence seizures have also been observed [2,9,10].…”

“…Its prevalence is estimated in 1-20,000 live births and mutations in the gene encoding cystatin B (CSTB), a cysteine protease inhibitor, are responsible for the EPM1 defects [1,3,[6][7][8].…”

“…Beyond these common characteristics and according to underlying disease, other clinical manifestations might be crucial for the etiological diagnosis, such as the existence of partial visual seizures in Lafora disease or the presence of myopathy, neuropathy or deafness, suggesting myoclonic epilepsy with ragged red fibers (MERRF) [1][2][3] Table 1.…”

“…They are also more apparent on the face and distal extremities. Massive bilateral myoclonus including the proximal muscles of the limbs may also occur [1][2][3].…”

“…The conditions include autosomal recessive Unverricht-Lundborg's disease (EPM1), Lafora disease (EPM2), neuronal ceroid lipofuscinosis and storage diseases such as sialidosis. Dentatorubralpallidoluysian atrophy (DRPLA) is a disease of trinucleotide repeat, whereas myoclonic epilepsy with ragged red fibers (MERRF) is an example of mitochondrial inheritance disease [1][2][3].…”