title: Lafora disease.
abstract: Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy due to mutations in the EPM2A (laforin) and EPM2B (malin) genes, with no substantial genotype-phenotype differences between the two. Founder effects and recurrent mutations are common, and mostly isolated to specific ethnic groups and/or geographical locations. Pathologically, LD is characterized by distinctive polyglucosans, which are formations of abnormal glycogen. Polyglucosans, or Lafora bodies (LB) are typically found in the brain, periportal hepatocytes of the liver, skeletal and cardiac myocytes, and in the eccrine duct and apocrine myoepithelial cells of sweat glands. Mouse models of the disease and other naturally occurring animal models have similar pathology and phenotype. Hypotheses of LB formation remain controversial, with compelling evidence and caveats for each hypothesis. However, it is clear that the laforin and malin functions regulating glycogen structure are key. With the exception of a few missense mutations LD is clinically homogeneous, with onset in adolescence. Symptoms begin with seizures, and neurological decline follows soon after. The disease course is progressive and fatal, with death occurring within 10 years of onset. Antiepileptic drugs are mostly non-effective, with none having a major influence on the progression of cognitive and behavioral symptoms. Diagnosis and genetic counseling are important aspects of LD, and social support is essential in disease management. Future therapeutics for LD will revolve around the pathogenesics of the disease. Currently, efforts at identifying compounds or approaches to reduce brain glycogen synthesis appear to be highly promising.
authors.affiliation: Program in Genetics and Genome Biology and Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Turnbull
authors.affiliation: Program in Genetics and Genome Biology and Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Canada.
authors.forename: Erica
authors.initials: E
authors.lastname: Tiberia
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 'G. Gaslini' Institute, Genova, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: Centre Saint-Paul, Hôpital Henri-Gastaut, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Genton
authors.affiliation: Department of Anatomic Pathology, Hospital Sao Joao, Porto, Portugal.
authors.forename: Stirling
authors.initials: S
authors.lastname: Carpenter
authors.affiliation: Division of Pathology, Department of Pathology and Laboratory Medicine, The Hospital for Sick Children and the University of Toronto, Canada.
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Ackerley
authors.affiliation: Program in Genetics and Genome Biology and Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Canada.
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005817:Genetic Counseling; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D020192:Lafora Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics
chemical_list: D006003:Glycogen; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human
keywords: EPM2A; EPM2B; Lafora; glycogen phosphatase; laforin; malin; progressive myoclonus epilepsies; ubiquitin