Unverricht-Lundborg disease (ULD; EPM1) and the neuronal ceroid lipofuscinoses (NCL; CLN) are clinically and genetically heterogeneous inherited neurodegenerative disorders characterized by myoclonus, epilepsy and progressive neurologic deterioration of varying degree. EPM1 is characterized by onset at age 6–16 years, stimulus-sensitive, action-activated myoclonus, epilepsy and ataxia. The main gene underlying EPM1, CSTB, encodes Cystatin B, a cysteine protease inhibitor. A Cystatin B –deficient mouse model for EPM1 has been created and characterized. Despite progress in understanding the biological function of CSTB, the disease mechanisms in EPM1 remain elusive. Mutations in two other genes, PRICKLE1 and SCARB2, have been reported in CSTB mutation negative patients presenting with symptoms closely resembling EPM1.
The NCLs are a group of disorders characterized by the accumulation of autofluorescent storage material in neurons and many other cell types. Clinical features display a variable age of onset and include cognitive decline, epilepsy and visual loss. Eight genes underlying human NCLs have now been identified (CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8 and CLN10) and two are predicted to exist but have not yet been isolated (CLN4, CLN9). A database of mutations is available (
Copyright © 2012, Michael A Rogawski, Antonio V Delgado-Escueta, Jeffrey L Noebels, Massimo Avoli and Richard W Olsen.