Lafora's disease: Towards a clinical, pathologic, and molecular synthesis

Lafora's disease is one of five inherited progressive myoclonus epilepsy sy ndromes. It is an autosomal-recessive disorder with onset in late childhood or adolescence. Characteristic seizures include myoclonic and occipital lo be seizures with visual hallucinations, scotomata, and photoconvulsions. Th e course of the disease consists of worsening seizures and an inexorable de cline in mental and other neurologic functions that result in dementia and death within 10 years of onset. Pathology reveals pathognomonic polyglucosa n inclusions that are not seen in any other progressive myoclonus epilepsy. Lafora's disease is one of several neurologic conditions associated with b rain polyglucosan bodies. Why Lafora's polyglucosan bodies alone are associ ated with epilepsy is unknown and is discussed in this article. Up to 80% o f patients with Lafora's disease have mutations in the EPM2A gene. Although common mutations are rare, simple genetic tests to identify most mutations have been established. At least one other still-unknown gene causes Lafora 's disease. The EPM2A gene codes for the protein laforin, which localizes a t the plasma membrane and the rough endoplasmic reticulum and functions as a dual-specificity phosphatase. Work toward establishing the connection bet ween laforin and Lafora's disease polyglucosans is underway, as are attempt s to replace it into the central nervous system of patients with Lafora's d isease. (C) 2001 by Elsevier Science Inc. All rights reserved.