Epilepsia, 45(9):1061–1063, 2004 Blackwell Publishing, Inc. C  2004 International League Against Epilepsy Univerricht-Lundborg Disease: Underdiagnosed in the Netherlands ∗ Gerrit-Jan de Haan, †Dicky J.J. Halley, ‡§Jan C. Doelman, ∗ Huibert H. Geesink, ∗ Paul B. Augustijn, ∗ Anke D. Jager-Jongkind, ‡Marianne Majoie, ∗ ∗∗ Adri J. Bader, ∗ Lian A.W.M. Leliefeld-ten Doeschate, †Wout H. Deelen, ∗ ‖Ed Bertram, ¶Anna E. Lehesjoki, and ∗∗ Dick Lindhout ∗ Epilepsy Institute of the Netherlands SEIN, Heemstede; †Department of Clinical Genetics, Erasmus Medical Center, Rotterdam; ‡Epilepsy Center Kempenhaeghe, Heeze; §Oosterscheldeziekenhuizen, Goes, the Netherlands; // Department of Neurology, F E Dreifuss Comprehensive Epilepsy Program, University of Virginia, Charlottesville, Virginia, U.S.A.; ¶ Folkh¨ alsan Institute of Genetics, Department of Medical Genetics and Neuroscience Center, Biomedicum Helsinki, University of Helsinki, Finland; and ∗∗ DBG-Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands 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 hypoth- esized that the syndrome may be underdiagnosed in patients with myoclonus epilepsy. Methods: Mutation analysis of the cystatin B gene was per- formed 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 previ- ous reports of ULD suggests that underdiagnosis of the syn- drome is likely. These findings also indicate that persons with juvenile-onset myoclonus epilepsy with action myoclonus should be analyzed for ULD. Key Words: Unverricht- Lundborg syndrome—Phenotype—Neurological diagnostic techniques. Progressive myoclonus epilepsies are a heteroge- neous group of inherited disorders, associated with my- oclonus, epilepsy, and progressive neurologic deteriora- tion. Univerricht-Lundborg disease (ULD) is the most common single cause of these disorders and occurs in any population or race (1). However, in the Netherlands and many western European countries, ULD is virtually unknown, possibly because of underdiagnosis or misdi- agnosis (2). The most common genetic defect associ- ated with the ULD phenotype is homozygosity for an expanded dodecamer repeat in the cystatin B (CSTB) gene, located on chromosome 21q22 (3). Point mutations also have been described in this gene in clinical ULD. The current study describes the first ULD patients in the Netherlands, confirming the occurrence in both native and immigrant populations and implying a high frequency of misdiagnosis. Accepted April 5, 2004. Address correspondence and reprint requests to Dr. G.J. de Haan at Epilepsy Institute of the Netherlands SEIN, P.O. Box 21, 2100 AA Heem- stede, The Netherlands. E-mail: gjdhaan@sein.nl METHODS A selection of patients attending regional Dutch epilepsy clinics were included in the study if they had symptomatic or cryptogenic epilepsy with action my- oclonus as a prominent feature or if they had juvenile myoclonic epilepsy (JME) with atypical features, such as myoclonus extending beyond the awakening period, med- ically refractory myoclonus, or a progressive course of the disease. Priority was given to patients with consan- guineous parentage. In total, 21 patients with intractable myoclonus or myoclonus epilepsy were referred for evaluation. Af- ter obtaining informed consent, patients and relatives were interviewed about seizure history and psychoso- cial situation. Medical records were consulted, and EEG recordings reviewed. An EEG with standardized photic stimulation protocol had been performed in 18 patients (4). Blood samples were obtained for analysis of the cystatin B(CSTB) gene. DNA analysis started with determination of the dodecamer repeat length in the CSTB gene. In pa- tients heterozygous for expansions, the coding regions of 1061