Autosomal recessive progressive myoclonus epilepsy with ataxia and mental retardation

Abstract

We describe two couples of sibs from a southern Italian family affected by epilepsy, myoclonus, mental retardation and slight ataxia. Onset was between 4 and 12 years and the course slowly progressive. The clinical picture suggested the diagnosis of Unverricht-Lundborg disease. Molecular study excluded linkage to EPM1. Other possible causes of progressive myoclonus epilepsy were also excluded.

Progressive myoclonic epilepsies

“…5,6 The patients in cluster 2 more often presented with severe myoclonus at onset, whereas epilepsy was less severe. A frequent positive family history in this group also supports the possibility that PME is a recessive trait in these patients, perhaps including a myoclonic variant of progressive cerebellar disease previously observed in a few families and individual subjects, [25][26][27] or a late phenotype of yet unknown genetic disorders.…”

Description of a family with a novel progressive myoclonus epilepsy and cognitive impairment

“…This family presents striking similarities with an Italian family described by Coppola et al25 They reported two ethnic Italians couples of sibs affected by rare GTCS (except in one patient with monthly frequency), myoclonus, mental retardation and slight ataxia with onset between 4 and 12 years and autosomal recessive transmission; an extensive diagnostic work‐up disclosed none of the known causes of PMEs.…”

“…In conclusion, we describe a family presenting a peculiar PME with probable autosomal recessive inheritance. Clinical and EEG data provided will help comparing this family to other published25 and unpublished reports, facilitating collaboration for genome wide scan of pooled DNA, hopefully leading to the identification of a new PME.…”

Cystatin B and its EPM1 mutants are polymeric and aggregate prone in vivo

“…On the other hand, the recent findings, concerning genes other than CSTB involved in the etiopathogenesis of the disease [64][65], suggest that the situation is more complex than envisaged so far and puts forward the existence of additional causative factors unrelated to the cystatin/cathepsin pathway in the pathogenesis of EPM1.…”

“…Recently, Berkovic et al [64] and Coppola et al [65] have described EPM1 cases in which the CSTB gene is not mutated and mutations of genes located on chromosomes others than 21 are the causative factors of the disease. The former authors [64] have studied an inbred Arab family with the clinical pattern of EPM1 and mapped the disease locus to the pericentromeric region of chromosome 12.…”