Major intra-familial variability in Unverricht-Lundborg disease
Corresponding Author
Amina Nasri
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Correspondence: Amina Nasri Riadh Gouider Department of Neurology, Razi University Hospital, 1 rue des Orangers, la Manouba, PC 2010, Tunis, Tunisia <[email protected]> <[email protected]>Search for more papers by this authorSabrina Zidi
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorImen Kacem
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorSaloua Mrabet
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorMouna Ben Djebara
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorAmina Gargouri
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorEric Leguern
Institut national de la santé et de la recherche médicale (INSERM), U975, ICM, Hôpital Pitié-Salpêtrière, Paris, Sorbonne Universités, Institut du Cerveau et de la Moelle épinière, ICM, Inserm U1127, CNRS UMR 7225, Paris, APHP, Hôpital Pitié-Salpêtrière, Département de Génétique, Paris, France
Search for more papers by this authorRiadh Gouider
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorCorresponding Author
Amina Nasri
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Correspondence: Amina Nasri Riadh Gouider Department of Neurology, Razi University Hospital, 1 rue des Orangers, la Manouba, PC 2010, Tunis, Tunisia <[email protected]> <[email protected]>Search for more papers by this authorSabrina Zidi
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorImen Kacem
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorSaloua Mrabet
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorMouna Ben Djebara
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorAmina Gargouri
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorEric Leguern
Institut national de la santé et de la recherche médicale (INSERM), U975, ICM, Hôpital Pitié-Salpêtrière, Paris, Sorbonne Universités, Institut du Cerveau et de la Moelle épinière, ICM, Inserm U1127, CNRS UMR 7225, Paris, APHP, Hôpital Pitié-Salpêtrière, Département de Génétique, Paris, France
Search for more papers by this authorRiadh Gouider
Neurology Department, LR18SP03, Razi University Hospital, 1 rue des Orangers Manouba, PC : 2010, Tunis, Tunisia
Faculty of Medicine of Tunis, University of Tunis El Manar, 15, Rue Djebel Akhdhar, La Rabta, 1007 Tunis, Tunisia
Clinical Investigation Center (CIC), Razi University Hospital, 1 rue des Orangers, la Manouba, PC : 2010, Tunis, Tunisia
Search for more papers by this authorAbstract
Unverricht-Lundborg disease (ULD), also called progressive myoclonic epilepsy type 1, is usually characterized by the presence of ataxia associated with myoclonus and epileptic seizures without progressive cognitive deficit, presenting during late childhood and early adolescence. Currently, there is a growing body of evidence for atypical presentations of the disease with a milder phenotype or without the full symptomatology. We describe a case report of a late-onset phenotype with progressive myoclonus-ataxia syndrome accompanied by initial recurrent falls, resulting in specific phobia and agoraphobia starting at the age of 50 years old. The examination revealed multifocal myoclonus with cerebellar ataxia and electroencephalogram showed generalized polyspikes and spike-wave discharges. Electromyogram revealed positive myoclonus of 60-ms duration in the face and the presence of C reflex. A genetic study confirmed the diagnosis of ULD in the patient and other additional family members, presenting a wide range of intra-familial variability. We discuss the challenging differential diagnosis for such a misleading presentation and its possible underlying pathophysiological mechanisms. Our case report may contribute to broadening the age and clinical boundaries for this disease and emphasizes the intra-familial age and symptom variability. Based on a suggestive family history, the diagnosis of ULD should be considered in this context, even in older patients.
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References
- 1Gargouri-Berrechid A., Nasri A., Kacem I., Sidhom Y., Abdelkefi I., Hizem Y. et al. Long-term evolution of EEG in Unverricht-Lundborg disease. Neurophysiol Clin. 46 (2) 2016; 119–124.
- 2Berrechid A.G., Bendjebara M., Bouteiller D., Nasri A., Peuvion J.N., Marie Y. et al. Juvenile myoclonic epilepsy phenotype in a family with Unverricht-Lundborg disease. Epileptic Disord. 21 (4) 2019; 359–365.
- 3Kälviäinen R., Khyuppenen J., Koskenkorva P., Eriksson K., Vanninen R., Mervaala E. Clinical picture of EPM1-Unverricht-Lundborg disease. Epilepsia. 49 (4) 2008; 549–556.
- 4Möller J.C., Hamer H.M., Oertel W.H., Rosenow F. Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS). Seizure. 11 (Suppl. A) 2002; 303–305.
- 5Chew N.K., Mir P., Edwards M.J., Cordivari C., Martino D., Schneider S.A. et al. The natural history of Unverricht-Lundborg disease: a report of eight genetically proven cases. Mov Disord. 23 (1) 2008; 107–113.
- 6Oi Y., Kobayashi K., Hitomi T., Matsumoto R., Ikeda A., Takahashi R. Low-dose perampanel improved cortical myoclonus and basophobia in a patient with Unverricht-Lundborg disease: a case report. Rinsho Shinkeigaku. 58 (10) 2018; 622–625.
- 7Könönen M., Danner N., Koskenkorva P., Kälviäinen R., Hyppönen J., Mervaala E. et al. Reduced cortical activation in inferior frontal junction in Unverricht-Lundborg disease (EPM1) – A motor fMRI study. Epilepsy Res. 1112015; 78–84.
- 8de Carvalho M.R., Velasques B.B., Freire R.C., Cagy M., Marques J.B., Teixeira S. et al. Frontal cortex absolute beta power measurement in panic disorder with agoraphobia patients. J Affect Disord. 1842015; 176–181.
- 9Gouider R., Ibrahim S., Fredj M., Gargouri A., Saïdi H., Ouezzani R. et al. Unverricht-Lündborg disease: clinical and electrophysiologic study of 19 Maghreb families. Rev Neurol (Paris). 154 (6-7) 1998; 503–507.
- 10Crespel A., Ferlazzo E., Franceschetti S., Genton P., Gouider R., Kälviäinen R. et al. Unverricht-Lundborg disease. Epileptic Disord. 18 (S2) 2016; 28–37.
- 11Lalioti M.D., Scott H.S., Genton P., Grid D., Ouazzani R., M'Rabet A. et al. A PCR amplification method reveals instability of the dodecamer repeat in progressive myoclonus epilepsy (EPM1) and no correlation between the size of the repeat and age at onset. Am J Hum Genet. 62 (4) 1998; 842–847.
- 12Hyppönen J., Äikiä M., Joensuu T., Julkunen P., Danner N., Koskenkorva P. et al. Refining the phenotype of Unverricht-Lundborg disease (EPM1): a population-wide Finnish study. Neurology. 84 (15) 2015; 1529–1536.
- 13Canafoglia L., Ferlazzo E., Michelucci R., Striano P., Magaudda A., Gambardella A. et al. Variable course of Unverricht-Lundborg disease: early prognostic factors. Neurology. 89 (16) 2017; 1691–1697.
- 14Canafoglia L., Ciano C., Panzica F., Scaioli V., Zucca C., Agazzi P. et al. Sensorimotor cortex excitability in Unverricht-Lundborg disease and Lafora body disease. Neurology. 63 (12) 2004; 2309–2315.
- 15Danner N., Säisänen L., Määttä S., Julkunen P., Hukkanen T., Könönen M. et al. Motor cortical plasticity is impaired in Unverricht-Lundborg disease. Mov Disord. 26 (11) 2011; 2095–2100.
- 16Kälviäinen R., Genton P., Andermann E., Andermann F., Magaudda A., Frucht S.J. et al. Brivaracetam in Unverricht-Lundborg disease (EPM1): results from two randomized, double-blind, placebo-controlled studies. Epilepsia. 57 (2) 2016; 210–221.
- 17Khiari H.M., Franceschetti S., Jovic N., Mrabet A., Genton P. Death in Unverricht-Lundborg disease. Neurol Sci. 30 (4) 2009; 315–318.
- 18Satishchandra P., Sinha S. Progressive myoclonic epilepsy. Neurol India. 58 (4) 2010; 514–522.
- 19Koskenkorva P., Niskanen E., Hyppönen J., Könönen M., Mervaala E., Soininen H. et al. Sensorimotor, visual, and auditory cortical atrophy in Unverricht-Lundborg disease mapped with cortical thickness analysis. AJNR Am J Neuroradiol. 33 (5) 2012; 878–883.
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