Epilepsy and movement disorders are found together in many clinical syndromes and a link at a molecular level is being increasingly recognized by the cloning of genes responsible for these conditions. Further evidence for the molecular overlap of movement disorders and epilepsy comes from genes cloned in mutant mice.

There are two major groups of disorders causing both movement disorders and epilepsy: neurodegenerative disorders and channelopathies.

In this chapter we will briefly review neurodegenerative conditions in which epilepsy and movement disorders are the predominant symptoms. The second part of this chapter will deal with the developing field of channelopathies. Over the past few years, several ion channel genes have been implicated in idiopathic epilepsy and paroxysmal movement disorders. In addition, the cloning of ion channels as the genes responsible for mouse mutants with epilepsy and movement disorders and the creation of mouse knockouts of specific genes, have emphasized the importance of this group of genes in the pathogenesis of these disorders.

Neurodegenerative disorders

Many neurodegenerative conditions have either epilepsy, or a movement disorder or both as a manifestation of disease in some individuals. In this chapter however, we will describe the genetic abnormalities in three diseases in which both epilepsy and movement disorders are prominent components of the phenotype.

Mitochondrial cytopathies

Mitochondrial disease is frequently associated with epilepsy, either generalized tonic-clonic events or myoclonic epilepsy.

Introduction

Paroxysmal dyskinesias (PDs) refer to relatively brief attacks of abnormal movements and postures with return to normal between episodes. The abnormal movements consist of dystonia, choreo-athetosis, and ballism, often in combination. The duration is variable, from very short attacks lasting a few seconds to prolonged ones, lasting several hours. The frequency is variable, as is the side of the body involved. PDs can be sporadic or familial with autosomal dominant inheritance or can be symptomatic of different conditions (Bressman et al., 1988; Fahn, 1994; Demirkiran & Jankovic, 1995).

Since the first description by Mount and Reback (1940), numerous reports of patients with PDs have followed and several classifications, based on duration of attacks and etiology have been proposed (Lance, 1977; Goodenough et al., 1978; Fahn, 1994). The most recent one classifies PDs according to the precipitating events and distinguishes the following forms: paroxysmal kinesigenic dyskinesias (PKD), paroxysmal non-kinesigenic dyskinesias (PNKD), paroxysmal exertioninduced dyskinesias (PED), paroxysmal hypnogenic dyskinesias (PHD) (Demirkiran & Jankovic, 1995).

The purpose of the chapter is to describe the clinical features of the classical forms of PDs including benign paroxysmal torticollis of infants (BPT) and paroxysmal tonic up-gaze deviation of infants (PTUDI) and to review the more recent data on pathophysiology of PDs as derived from genetic studies and from animal model.

Clinical features

Paroxysmal kinesigenic dyskinesia (PKD)

Most cases of PKD are idiopathic, both familial with autosomal dominant pattern of inheritance or sporadic, but cases of symptomaticPKDare reported (Fahn, 1994; Marsden, 1996; Demirkiran & Jankovic, 1995; Hwang et al., 1998).