Progressive myoclonus epilepsy: genetic and nosological aspects with special reference to 107 Finnish patients

Abstract

In 107 Finnish patients with progressive myoclonus epilepsy (PME), belonging to 74 families, autosomal recessive inheritance was evident. The sex ratio was 48:51, the corrected proportion of affected sibs being 0.260. Of 68 marriages 15, or 22 %, were consanguineous; several of the parents were related and the geographical distribution was of the uneven type typical of young, isolated populations in Finland. The incidence in Finland was estimated to exceed 1:20,000. The clinical picture in the Finnish PME patients was uniform, being identical with that of Unverricht's and Lundborg's patients, but clearly distinct from Lafora disease. The following classification of PME is proposed: (1) PME, Lafora type: onset of grand mal attacks and/or myoclonus around the 15th year of life; rapid and severe mental deterioration, often with psychotic symptoms; short survival; histological finding of Lafora bodies; autosomal recessive inheritance. (2) PME, Unverricht‐Lundborg type: onset around the 10th year of life; severity variable, progressive invalidity from myoclonic features associated with mild mental symptoms, time of survival variable, “degenerative” histological changes; autosomal recessive inheritance. (3) Autosomal dominant or otherwise atypical cases of PME. The importance of accurate diagnosis is stressed.

Severer Phenotype in Unverricht-Lundborg Disease (EPM1) Patients Compound Heterozygous for the Dodecamer Repeat Expansion and the c.202C>T Mutation in the <i>CSTB</i> Gene

“…Moreover, patients carrying such a mutation are more likely to have a severer form of the disease resulting in severer myoclonus and treatment-resistant epileptic seizures. It has previously been reported that in EPM1, the epileptic seizures have a positive response to antiepileptic drug treatment [16] and tend to decrease in frequency or cease completely within 10-15 years from the onset of the disease [2,17] . We found that 3 of the compound heterozygous patients, with a disease duration of over 10 years, were still suffering from tonicclonic seizures despite extensive antiepileptic drug treatment.…”

“…128, FOV 256 ! 256 mm 2 , 73 axial slices with slice thickness of 2 mm) with diffusion gradients (b-values 0 and 1,000 s/mm 2 ) applied in 30 directions.…”

“…The prevalence of EPM1 is increased around the Baltic Sea, especially in Finland [2] , and also in the western Mediterranean region [3] . Currently, there are over 150 genetically verified EPM1 cases in Finland and about 3 new cases are diagnosed each year.…”

Progressive myoclonic epilepsies: review of clinical, molecular and therapeutic aspects

“…Its prevalence is estimated in 1-20,000 live births and mutations in the gene encoding cystatin B (CSTB), a cysteine protease inhibitor, are responsible for the EPM1 defects [1,3,[6][7][8].…”

Cystatin C Rescues Degenerating Neurons in a Cystatin B-Knockout Mouse Model of Progressive Myoclonus Epilepsy

“…UnverrichtLundborg disease (EPM1), the most common form of progressive myoclonus epilepsy, is a rare autosomal disorder caused by loss-of-function mutations in the gene encoding cystatin B (CysB). [1][2][3] EPM1 has an onset of symptoms at 6 to 15 years of age, and progression with age leads to myoclonic and tonic-clonic seizures, 4,5 neurological decline, and severe ataxia. 4,6 CysB, a member of the cystatin family 1 of cysteine protease inhibitors, is mainly found in the cytosol and at lower levels in body fluids.…”