Unverricht-Lundborg disease (ULD) is the purest and least severe type of progressive myoclonus epilepsy (PME), and is not associated with progressive cognitive deficit. It evolves towards a stabilization of symptoms in adulthood, with a varying degree of permanent, often severe, handicap that is mostly due to myoclonus. Onset occurs between the ages of 8 and 15 years with generalized tonic-clonic or clonic-tonic-clonic seizures, action myoclonus (massive or segmental), photosensitivity, and often ataxia. Prevalence varies and is highest in certain geographic isolates (Finland, La Réunion Island) and in regions with a higher degree consanguinity (Maghreb). ULD follows an autosomal recessive transmission pattern and is due to a deficit in cystatin B (stefin B), but the mechanisms leading to the clinical symptoms are not well understood. The causative gene, EPM1, was localized in 1991 to chromosome 21q22.3 and was found to carry rare point mutations and, more commonly, expansions of the CCCCGCCCCGCG dodecamer. A variant has been recently reported in a Palestinian family, with localization on chromosome 12. The diagnosis of ULD is made on the basis of family history, age at onset, the geographical and ethnic context, and on the typical features of myoclonus and epilepsy, in the absence of cognitive and sensory deficits. Neurophysiological evaluation yields interesting, but unspecific results. There are no biological or pathological markers for ULD. Molecular biology easily confirms the diagnosis in most patients. Genetic counseling and even prenatal diagnosis are possible, although seldom performed, if the mutation has been identified. In spite of intensive research, certain features of ULD remain to be understood. It remains a quasi ``idiopathic'' type of PME, with limited progression. Clinicians and patients are still expecting an etiologically oriented treatment, which should, ideally, be administered early in the course of the disease, if possible before theonset of invalidating symptoms.
Last update: July 2006