Lafora disease

Lafora disease (also known as Lafora progressive myoclonus epilepsy or EPM2) is a rare, severe form of progressive myoclonus epilepsy that typically begins in late childhood or adolescence, usually between the ages of 6 and 18 years. It is characterized by the accumulation of abnormal glycogen inclusions called Lafora bodies in neurons, muscle cells, liver, skin, and other tissues. The disease is caused by mutations in the EPM2A gene (encoding laforin) or the NHLRC1/EPM2B gene (encoding malin), both of which play critical roles in glycogen metabolism and protein quality control. The hallmark clinical features of Lafora disease include stimulus-sensitive myoclonic seizures, generalized tonic-clonic seizures, occipital seizures (which may present with transient blindness or visual hallucinations), and progressive, relentless cognitive decline leading to dementia. Cerebellar ataxia, dysarthria, and psychiatric symptoms including depression and behavioral changes are also common. The disease follows a devastating course, with progressive neurological deterioration that typically leads to a state of continuous myoclonus, refractory epilepsy, and severe dementia. Most affected individuals become dependent for all activities of daily living within approximately 10 years of onset, and the disease is usually fatal within a decade of symptom onset. Currently, there is no cure or disease-modifying treatment for Lafora disease. Management is primarily supportive and symptomatic, focusing on seizure control with antiepileptic medications such as valproate, benzodiazepines, levetiracetam, and perampanel. Certain antiepileptic drugs, particularly sodium channel blockers like carbamazepine and phenytoin, may worsen myoclonus and should generally be avoided. Research into potential therapies, including gene therapy, antisense oligonucleotides targeting glycogen synthase, and enzyme replacement strategies, is ongoing but remains in preclinical or early clinical stages. Genetic counseling is recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Lafora disease