Univerricht‐Lundborg Disease: Underdiagnosed in the Netherlands

Abstract

Summary:Purpose: Univerricht-Lundborg disease (ULD), with its major symptom of action myoclonus, is supposed to be very rare in the Netherlands and western Europe. We hypothesized that the syndrome may be underdiagnosed in patients with myoclonus epilepsy.Methods: Mutation analysis of the cystatin B gene was performed in 21 cases with uncontrolled myoclonus.Results: Seven of the 21 evaluated cases carried mutations in the cystatin B gene. Diagnosis of ULD was made with a mean delay of 20 years from symptom onset.Conclusions: This study from a country without previous reports of ULD suggests that underdiagnosis of the syndrome is likely. These findings also indicate that persons with juvenile-onset myoclonus epilepsy with action myoclonus should be analyzed for ULD.

Loss of lysosomal association of cystatin B proteins representing progressive myoclonus epilepsy, EPM1, mutations

“…A novel missense mutation, g.2398A4C, found in compound heterozygous form with the minisatellite expansion, results in the substitution of a glutamine at position 71 by a proline (p.Gln71Pro). 11 Although CSTB has been shown to function in vitro as a reversible inhibitor of cathepsins B, H, L and S, 13,14 its physiological function remains unknown. In EPM1 patient lymphoblastoid cells decreased CSTB inhibitory activity correlates with enhanced activity of cathepsins B, L and S, demonstrating that cathepsin activity is regulated by CSTB also in vivo.…”

Clinical picture of EPM1‐Unverricht‐Lundborg disease

“…EPM1 is also the major cause of PME in North America, but exact prevalence figures are not available (Eldridge et al, 1983; Berkovic et al, 1986; Lehesjoki et al, 1993). However, the study recently carried out in The Netherlands (de Haan et al, 2004) has suggested that it is likely that EPM1 may be underdiagnosed in many countries. This view is further supported by the fact that sporadic cases have been diagnosed worldwide.…”

Unverricht-Lundborg Disease: A Case Report and Literature Review

“…Valproate should be tried as the first option. Another effective drug that may be used in the early stages is levetiracetam [29]. Primidone and high-dose of piracetam are useful in myoclonic seizures.…”