CLINICAL-FEATURES AND GENETICS OF PROGRESSIVE MYOCLONUS EPILEPSY OF THE UNVERRICHT-LUNDBORG TYPE

Progressive myoclonus epilepsy of the Unverricht-Lundborg type is the most common cause of progressive myoclonus epilepsy worldwide. Typical features include onset at the age of 6-15 years, stimulus-sensitive m yoclonus, tonic-clonic seizures, a progressive course and characterist ic electroencephalographic findings with an exceptionally high sensiti vity to photic stimulation. With modern anticonvulsive therapy the sym ptoms are relatively well controlled, and the disease may not always p rogress. Previously, no biochemical or pathological marker existed for the diagnosis of Unverricht-Lundborg disease. The positional cloning strategy was applied to identify the genetic defects that are responsi ble for this disease. The underlying gene encodes cystatin B, a cystei ne protease inhibitor. The major mutation worldwide is an unstable exp ansion of a dodecamer minisatellite repeat unit in the promoter region of the cystatin B gene. In addition, five 'minor' mutations have been described. In the majority of patients, a reduced level of the cystat in B gene product seems to be the primary mechanism in the pathology, but the pathogenetic mechanisms are yet unknown. The molecular genetic findings have made a specific diagnosis possible and are the basis fo r understanding the molecular pathogenesis of the disease. This unders tanding may lead to the development of specific therapies for Unverric ht-Lundborg disease.