Progressive Myoclonus Epilepsy, Lafora Type

Clinical characteristics: Progressive myoclonus epilepsy, Lafora type (also known as Lafora disease [LD]) is characterized by focal occipital seizures presenting as transient blindness or visual hallucinations and fragmentary, symmetric, or generalized myoclonus beginning in previously healthy individuals at age eight to 19 years (peak 14-16 years). Generalized tonic-clonic seizures, atypical absence seizures, atonic seizures, and focal seizures with impaired awareness may occur. The course of the disease is characterized by increasing frequency and intractability of seizures. Status epilepticus with any of the seizure types is common. Cognitive decline becomes apparent at or soon after the onset of seizures. Dysarthria and ataxia appear early while spasticity appears late. Emotional disturbance and confusion are common in the early stages of the disease and are followed by dementia. Most affected individuals die within ten years of onset, usually from status epilepticus or from complications related to nervous system degeneration.

Diagnosis/testing: The diagnosis of Lafora disease is established in a proband with characteristic neurologic findings and/or biallelic pathogenic variants in one of the two known causative genes, EPM2A or NHLRC1, identified on molecular genetic testing. On rare occasion skin biopsy to detect Lafora bodies is necessary to confirm the diagnosis.

Management: Treatment of manifestations: Medical treatment in combination with physical therapy and psychosocial support. Regular evaluation and readjustment are required as the disease progresses. Antiepileptic drugs are effective against generalized seizures, but do not influence the progression of cognitive and behavioral symptoms. Overmedication in treating drug-resistant myoclonus is a risk. Gastrostomy feedings can decrease the risk of aspiration pneumonia when disease is advanced.

Surveillance: Clinical and psychosocial evaluation at three- to six-month intervals throughout the teenage years.

Agents/circumstances to avoid: Phenytoin; possibly lamotrigine, carbamazepine, and oxcarbazepine.

Genetic counseling: Lafora disease is inherited in an autosomal recessive manner. Heterozygotes (carriers) are asymptomatic and not at risk of developing the disorder. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for at-risk pregnancies, and preimplantation genetic testing are possible if the pathogenic variants in the family are known.