Introduction

Progressive myoclonus epilepsies (PMEs) are a heterogeneous group of rare genetic disorders sharing a common clinical picture: myoclonus, epileptic seizures and signs of neurological deterioration, particularly dementia and ataxia (Marseille Consensus Group, 1990). The causes of the PME syndrome are many; most of them, however, can now be accurately diagnosed in life due to recent advances in pathology, biochemistry and molecular genetics (Berkovic et al., 1986; Roger et al., 1992). In particular, molecular genetics has most dramatically increased our knowledge of the basic mechanisms involved in the PMEs (Serratosa et al., 1999a). In order to establish a precise diagnosis, knowledge of the biochemical and molecular genetic bases of the PMEs must now complement experience in identifying the clinical, neuropathological, and neurophysiological characteristics of each PME.

Aside from the problems of diagnosis, there are still some unresolved issues concerning the neurophysiology and pathophysiology of some clinical features, like myoclonus, which contribute in different ways to the movement disorder and disability associated with the PME syndrome (Commission on Pediatric Epilepsy of the ILAE, 1997).

In this chapter we will outline the main specific disorders causing PME, along with the recent advances of molecular genetics contributing to the nosology and knowledge of these conditions. Finally, we will also address the issues of the clinical and neurophysiological aspects of PMEs, with special reference to three outstanding features of the syndrome: seizures, myoclonus and cerebellar dysfunction.

Specific disorders causing PME

Despite a large number of rare conditions that may present with a PME syndrome, five principal causes are responsible for most cases of PME worldwide: Unverricht–Lundborg disease, Lafora disease, mitochondrial encephalomyopathies, neuronal ceroidlipofuscinoses and sialidosis.