Lafora Disease

Progressive myoclonic epilepsies are rare genetic disorders that most frequently present in late childhood or adolescence but can be seen in all age groups from infancy to adulthood. Conversely, epileptic encephalopathies start with polymorphic seizures in early infancy. These epilepsies are associated with progressive myoclonus, epileptic seizures, dementia ataxia, and, in the worst cases, death. Progressive myoclonic epilepsies include Unverricht-Lundborg disease, Lafora disease, neuronal ceroid lipofuscinoses, sialidosis type I, myoclonus epilepsy, ragged red fibers (MERRF), Gaucher disease type 3, dentatorubral-pallidoluysian atrophy, and other rare progressive myoclonic epilepsies.

Lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy commonly observed in previously healthy adolescents, with death occurring within 10 years of symptom onset. Genetic research has identified many hereditary etiologies, and others are expected to be found. In Lafora disease, the main cause is the loss-of-function mutations in EPM2A and NHLRC1 that encode laforin and malin, respectively. Lack of either protein results in poorly branched, hyperphosphorylated glycogen that precipitates, aggregates, and accumulates into Lafora bodies. The presence of the pathognomic Lafora bodies in a tissue biopsy is diagnostic of Lafora disease.

Characteristic features of Lafora disease include intractable myoclonic and photosensitive seizures, drop attacks, ataxia, apraxia, cortical blindness, rapidly progressive dementia, and neuropsychiatric symptoms. Pathologically, Lafora disease is associated with polyglucosan deposits, also known as Lafora bodies, in the brain, liver, muscles, and sweat glands. This disease is diagnosed through clinical, electrophysiological, histological, and genetic findings. No curative treatments or preventative interventions are available at present for Lafora disease. Management Lafora disease focuses on symptomatic relief of seizures and myoclonus, together with palliative, supportive, and rehabilitative measures. Antiepileptic drugs can be used for the management of myoclonus and seizures. However, patients can become drug-resistant over time, resulting in disease progression, increased seizure frequency, and a decline in neurologic function.