Lafora's disease: towards a clinical, pathologic, and molecular synthesis.
Lafora's disease is one of five inherited progressive myoclonus epilepsy syndromes. It is an autosomal-recessive disorder with onset in late childhood or adolescence. Characteristic seizures include myoclonic and occipital lobe seizures with visual hallucinations, scotomata, and photoconvulsions. The course of the disease consists of worsening seizures and an inexorable decline in mental and other neurologic functions that result in dementia and death within 10 years of onset. Pathology reveals pathognomonic polyglucosan inclusions that are not seen in any other progressive myoclonus epilepsy. Lafora's disease is one of several neurologic conditions associated with brain polyglucosan bodies. Why Lafora's polyglucosan bodies alone are associated with epilepsy is unknown and is discussed in this article. Up to 80% of 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 at the plasma membrane and the rough endoplasmic reticulum and functions as a dual-specificity phosphatase. Work toward establishing the connection between laforin and Lafora's disease polyglucosans is underway, as are attempts to replace it into the central nervous system of patients with Lafora's disease.
Minassian
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BA
Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and The University of Toronto, M5G 1X8, Toronto, Ontario, Canada.
D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D003937:Diagnosis, Differential; D004569:Electroencephalography; D005936:Glucans / Q000378:metabolism*; D006801:Humans; D020192:Lafora Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008959:Models, Neurological; D009154:Mutation; D020191:Myoclonic Epilepsies, Progressive / Q000175:diagnosis; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor
D005936:Glucans; C083094:polyglucosan; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human