Progressive Myoclonus Epilepsy, Lafora Type

CLINICAL CHARACTERISTICS

Progressive myoclonus epilepsy, Lafora type (also known as Lafora disease) is characterized by focal occipital seizures presenting as transient blindness or visual hallucinations and fragmentary, symmetric, or generalized myoclonus occurring in previously healthy individuals. Typical age of onset is eight to 19 years (peak: age14-16 years). Generalized tonic-clonic seizures, atypical absence seizures, atonic seizures, and focal seizures with impaired awareness may also 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 disturbances 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 neurologic 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, or , identified by molecular genetic testing. On rare occasion, a skin biopsy to detect Lafora bodies is necessary to confirm the diagnosis.

MANAGEMENT

Medical treatment in combination with physical therapy and psychosocial support. Regular evaluation and readjustment are required as the disease progresses. Anti-seizure medications are effective against generalized seizures but do not alter the progression of cognitive and behavioral manifestations. Overmedication in treating drug-resistant myoclonus is a risk. Gastrostomy feedings can decrease the risk of aspiration pneumonia when the disease is advanced. Clinical and psychosocial evaluations throughout the teenage years. Monitoring of developmental progress and educational needs, in conjunction with behavioral assessments. Continuous assessment of feeding, nutritional status, and airway protection (including aspiration risk). Phenytoin as maintenance therapy; possibly lamotrigine, carbamazepine, and oxcarbazepine.

GENETIC COUNSELING

Lafora disease is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an or pathogenic variant, each sib of an affected individual has at conception 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.