Genetic analysis of the 5q34 locus for juvenile myoclonic epilepsy

Abstract

Epilepsy is a neurological condition characterised by occurrence of recurrent seizures. It usually manifests with diverse clinical symptoms which, involve motor, sensory, cognitive and autonomic alterations with or without loss of consciousness. The word epilepsy is derived from the Greek verb epilamvanein that means ‘to be seized or attacked’. This term originated from the notion that an epileptic episode symbolised periods of demonic possession. Medical records as early as 400 BC mention their occurrence and refer to epilepsy, reverentially as ‘sacred disease’ since supernatural mechanisms were thought to be at play. Modern concepts of epilepsy were enunciated by John Hughlings Jackson in the mid-19th century, when he proposed the idea that seizures were of different types and have their respective pathophysiology and semiology (Emery and Rimoin 2006, Engel and Pedley 1998). An epileptic seizure represents hyper-synchronous neuronal activity in the brain resulting in improper processing of electrical signals leading to abnormal functioning of the nervous system. Neuro-physiological intracellular recordings indicate deregulation of the mechanism that control membrane depolarization and repolarisation. Neural network defects due to atypical neuronal integration leading to spread of excitation along different pathways and defects in counterbalancing inhibitory processes are observed in seizure episodes. This is manifest as an epileptic spike on an electroencephalogram (EEG) indicating spontaneous occurrence of large amplitude synchronous depolarization (PDS: paroxysmal depolarization shift) that is used to diagnose epilepsy (Emery and Rimoin 2006, Engel and Pedley 1998, Shorvon 2011). Epilepsy is common and affects about 1% of the world population (Hauser et al 1993, Kaneko et al 2002). It is heterogeneous in origin