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31 results on '"De Jonghe, Peter"'

1. The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on MME

Author

Senderek, Jan, Lassuthova, Petra, Kabzińska, Dagmara, Abreu, Lisa, Baets, Jonathan, Beetz, Christian, Braathen, Geir J., Brenner, David, Dalton, Joline, Dankwa, Lois, Deconinck, Tine, De Jonghe, Peter, Dräger, Bianca, Eggermann, Katja, Ellis, Melina, Fischer, Carina, Stojkovic, Tanya, Herrmann, David N., Horvath, Rita, Høyer, Helle, Iglseder, Stephan, Kennerson, Marina, Kinslechner, Katharina, Kohler, Jennefer N., Kurth, Ingo, Laing, Nigel G., Lamont, Phillipa J., N. Löscher, Wolfgang, Ludolph, Albert, Marques, Wilson, Jr, Nicholson, Garth, Ong, Royston, Petri, Susanne, Ravenscroft, Gianina, Rebelo, Adriana, Ricci, Giulia, Rudnik-Schöneborn, Sabine, Schirmacher, Anja, Schlotter-Weigel, Beate, Schoels, Ludger, Schüle, Rebecca, Synofzik, Matthis, Francou, Bruno, Strom, Tim M., Wagner, Johannes, Walk, David, Wanschitz, Julia, Weinmann, Daniela, Weishaupt, Jochen, Wiessner, Manuela, Windhager, Reinhard, Young, Peter, Züchner, Stephan, Toegel, Stefan, Seeman, Pavel, Kochański, Andrzej, and Auer-Grumbach, Michaela

Published
2020
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3. Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Author

Coarelli, Giulia, Schule, Rebecca, van de Warrenburg, Bart P.C., De Jonghe, Peter, Ewenczyk, Claire, Martinuzzi, Andrea, Synofzik, Matthis, Hamer, Elisa G., Baets, Jonathan, Anheim, Mathieu, Schöls, Ludger, Deconinck, Tine, Masrori, Pegah, Fontaine, Bertrand, Klockgether, Thomas, DʼAngelo, Maria Grazia, Monin, Marie-Lorraine, De Bleecker, Jan, Migeotte, Isabelle, Charles, Perrine, Bassi, Maria Teresa, Klopstock, Thomas, Mochel, Fanny, Ollagnon-Roman, Elisabeth, DʼHooghe, Marc, Kamm, Christoph, Kurzwelly, Delia, Papin, Melanie, Davoine, Claire-Sophie, Banneau, Guillaume, Tezenas du Montcel, Sophie, Seilhean, Danielle, Brice, Alexis, Duyckaerts, Charles, Stevanin, Giovanni, and Durr, Alexandra

Published
2019
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4. Ataxia And Cough Are Indicative For Biallelic RFC1 Repeat Expansions In Hereditary Sensory And Autonomic Neuropathy (S29.010)

Author

Beijer, Danique, primary, Dohrn, Maike, additional, De Winter, Jonathan, additional, Fazal, Sarah, additional, Cortese, Andrea, additional, Stojkovic, Tanya, additional, Fernandez-Eulate, Gorka, additional, Gentile, Mattia, additional, Remiche, Gauthier, additional, Synofzik, Matthis, additional, De Jonghe, Peter, additional, Züchner, Stephan, additional, and Baets, Jonathan, additional

Published
2022
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5. Multisystem proteinopathy due to a homozygous p.Arg159His VCP mutation

Author

De Ridder, Willem, primary, Azmi, Abdelkrim, additional, Clemen, Christoph S., additional, Eichinger, Ludwig, additional, Hofmann, Andreas, additional, Schröder, Rolf, additional, Johnson, Katherine, additional, Töpf, Ana, additional, Straub, Volker, additional, De Jonghe, Peter, additional, Maudsley, Stuart, additional, De Bleecker, Jan L., additional, and Baets, Jonathan, additional

Published
2019
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6. Delineating the GRIN1 phenotypic spectrum

Author

Lemke, Johannes R., Geider, Kirsten, Helbig, Katherine L., Heyne, Henrike O., Schütz, Hannah, Hentschel, Julia, Courage, Carolina, Depienne, Christel, Nava, Caroline, Heron, Delphine, Møller, Rikke S., Hjalgrim, Helle, Lal, Dennis, Neubauer, Bernd A., Nürnberg, Peter, Thiele, Holger, Kurlemann, Gerhard, Arnold, Georgianne L., Bhambhani, Vikas, Bartholdi, Deborah, Pedurupillay, Christeen Ramane J., Misceo, Doriana, Frengen, Eirik, Strømme, Petter, Dlugos, Dennis J., Doherty, Emily S., Bijlsma, Emilia K., Ruivenkamp, Claudia A., Hoffer, Mariette J.V., Goldstein, Amy, Rajan, Deepa S., Narayanan, Vinodh, Ramsey, Keri, Belnap, Newell, Schrauwen, Isabelle, Richholt, Ryan, Koeleman, Bobby P.C., Sá, Joaquim, Mendonça, Carla, de Kovel, Carolien G.F., Weckhuysen, Sarah, Hardies, Katia, De Jonghe, Peter, De Meirleir, Linda, Milh, Mathieu, Badens, Catherine, Lebrun, Marine, Busa, Tiffany, Francannet, Christine, Piton, Amélie, Riesch, Erik, Biskup, Saskia, Vogt, Heinrich, Dorn, Thomas, Helbig, Ingo, Michaud, Jacques L., Laube, Bodo, and Syrbe, Steffen

Subjects
Heterozygote, Movement Disorders, Homozygote, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, Article, Cohort Studies, Consanguinity, Xenopus laevis, Phenotype, Seizures, Intellectual Disability, Mutation, Oocytes, Animals, Humans
Abstract

Objective: To determine the phenotypic spectrum caused by mutations in GRIN1 encoding the NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology. Methods: We collected molecular and clinical data from several diagnostic and research cohorts. Functional consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes. Results: We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity with a dominant-negative effect. In addition, we describe 2 homozygous GRIN1 mutations (1 missense, 1 truncation), each segregating with severe neurodevelopmental phenotypes in consanguineous families. Conclusions: De novo GRIN1 mutations are associated with severe intellectual disability with cortical visual impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1-associated disorders.

Published
2016

7. DNM1 encephalopathy : a new disease of vesicle fission

Author

von Spiczak, Sarah, Helbig, Katherine L., Shinde, Deepali N., De Jonghe, Peter, Weckhuysen, Sarah, Epi4K Consortium, and EuroEPINOMICS-RES NLES Working Group

Subjects
Human medicine, Biology
Abstract

Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. Methods: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. Results: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. Conclusions: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.

Published
2018

9. Phenotypic spectrum of GABRA1

Author

Johannesen, Katrine, primary, Marini, Carla, additional, Pfeffer, Siona, additional, Møller, Rikke S., additional, Dorn, Thomas, additional, Niturad, Cristina Elena, additional, Gardella, Elena, additional, Weber, Yvonne, additional, Søndergård, Marianne, additional, Hjalgrim, Helle, additional, Nikanorova, Mariana, additional, Becker, Felicitas, additional, Larsen, Line H.G., additional, Dahl, Hans A., additional, Maier, Oliver, additional, Mei, Davide, additional, Biskup, Saskia, additional, Klein, Karl M., additional, Reif, Philipp S., additional, Rosenow, Felix, additional, Elias, Abdallah F., additional, Hudson, Cindy, additional, Helbig, Katherine L., additional, Schubert-Bast, Susanne, additional, Scordo, Maria R., additional, Craiu, Dana, additional, Djémié, Tania, additional, Hoffman-Zacharska, Dorota, additional, Caglayan, Hande, additional, Helbig, Ingo, additional, Serratosa, Jose, additional, Striano, Pasquale, additional, De Jonghe, Peter, additional, Weckhuysen, Sarah, additional, Suls, Arvid, additional, Muru, Kai, additional, Talvik, Inga, additional, Talvik, Tiina, additional, Muhle, Hiltrud, additional, Borggraefe, Ingo, additional, Rost, Imma, additional, Guerrini, Renzo, additional, Lerche, Holger, additional, Lemke, Johannes R., additional, Rubboli, Guido, additional, and Maljevic, Snezana, additional

Published
2016
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10. Clinical Evidence for Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion (S21.006)

Author

Van Mossevelde, Sara, primary, Van Der Zee, Julie, additional, Gijselinck, Ilse, additional, Sleegers, Kristel, additional, Van Langenhove, Tim, additional, Sieben, Anne, additional, De Bleecker, Jan, additional, Ivanoiu, Adrian, additional, Deryck, Olivier, additional, Santens, Patrick, additional, Baumer, Veerle, additional, Van Den Broeck, Marleen, additional, Mattheijssens, Maria, additional, Peeters, Karin, additional, De Jonghe, Peter, additional, De Deyn, Peter, additional, Cras, Patrick, additional, Vandenberghe, Rik, additional, Martin, Jean-Jacques, additional, Cruts, Marc, additional, Engelborghs, Sebastiaan, additional, and Van Broeckhoven, Christine, additional

Published
2016
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11. Clinical Features of TBK1 Carriers and Comparison with C9orf72, GRN and Nonmutation Carriers in a Belgian Patient Cohort (S21.007)

Author

Van Mossevelde, Sara, primary, Van Der Zee, Julie, additional, Gijselinck, Ilse, additional, Engelborghs, Sebastiaan, additional, Sieben, Anne, additional, Van Langenhove, Tim, additional, De Bleecker, Jan, additional, Baets, Jonathan, additional, Vandenbulcke, Mathieu, additional, Van Laere, Koen, additional, Ceyssens, Sarah, additional, Van Den Broeck, Marleen, additional, Peeters, Karin, additional, Mattheijssens, Maria, additional, Cras, Patrick, additional, Vandenberghe, Rik, additional, De Jonghe, Peter, additional, Martin, Jean-Jacques, additional, De Deyn, Peter, additional, Cruts, Marc, additional, and Van Broeckhoven, Christine, additional

Published
2016
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12. STXBP1encephalopathy

Author

Stamberger, Hannah, primary, Nikanorova, Marina, additional, Willemsen, Marjolein H., additional, Accorsi, Patrizia, additional, Angriman, Marco, additional, Baier, Hartmut, additional, Benkel-Herrenbrueck, Ira, additional, Benoit, Valérie, additional, Budetta, Mauro, additional, Caliebe, Almuth, additional, Cantalupo, Gaetano, additional, Capovilla, Giuseppe, additional, Casara, Gianluca, additional, Courage, Carolina, additional, Deprez, Marie, additional, Destrée, Anne, additional, Dilena, Robertino, additional, Erasmus, Corrie E., additional, Fannemel, Madeleine, additional, Fjær, Roar, additional, Giordano, Lucio, additional, Helbig, Katherine L., additional, Heyne, Henrike O., additional, Klepper, Joerg, additional, Kluger, Gerhard J., additional, Lederer, Damien, additional, Lodi, Monica, additional, Maier, Oliver, additional, Merkenschlager, Andreas, additional, Michelberger, Nina, additional, Minetti, Carlo, additional, Muhle, Hiltrud, additional, Phalin, Judith, additional, Ramsey, Keri, additional, Romeo, Antonino, additional, Schallner, Jens, additional, Schanze, Ina, additional, Shinawi, Marwan, additional, Sleegers, Kristel, additional, Sterbova, Katalin, additional, Syrbe, Steffen, additional, Traverso, Monica, additional, Tzschach, Andreas, additional, Uldall, Peter, additional, Van Coster, Rudy, additional, Verhelst, Helene, additional, Viri, Maurizio, additional, Winter, Susan, additional, Wolff, Markus, additional, Zenker, Martin, additional, Zoccante, Leonardo, additional, De Jonghe, Peter, additional, Helbig, Ingo, additional, Striano, Pasquale, additional, Lemke, Johannes R., additional, Møller, Rikke S., additional, and Weckhuysen, Sarah, additional

Published
2016
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13. Loss ofTBK1is a frequent cause of frontotemporal dementia in a Belgian cohort

Author

Gijselinck, Ilse, primary, Van Mossevelde, Sara, additional, van der Zee, Julie, additional, Sieben, Anne, additional, Philtjens, Stéphanie, additional, Heeman, Bavo, additional, Engelborghs, Sebastiaan, additional, Vandenbulcke, Mathieu, additional, De Baets, Greet, additional, Bäumer, Veerle, additional, Cuijt, Ivy, additional, Van den Broeck, Marleen, additional, Peeters, Karin, additional, Mattheijssens, Maria, additional, Rousseau, Frederic, additional, Vandenberghe, Rik, additional, De Jonghe, Peter, additional, Cras, Patrick, additional, De Deyn, Peter P., additional, Martin, Jean-Jacques, additional, Cruts, Marc, additional, and Van Broeckhoven, Christine, additional

Published
2015
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14. Aggregates of Mutant DNMT1 Are Linked to a Spectrum of Neurological Disorders (S34.007)

Author

Baets, Jonathan, primary, Duan, Xiaohui, additional, Wu, Yanhong, additional, Smith, Gordon, additional, Seeley, William, additional, Mademan, Ines, additional, McGrath, Nicole, additional, Beadell, Noah, additional, Khoury, Julie, additional, Botuyan, Maria-Victoria, additional, Mer, Georges, additional, Worrell, Gregory, additional, Hojo, Kaori, additional, Delone, Jessica, additional, Laura, Matilde, additional, Liu, Yo-Tsen, additional, Senderek, Jan, additional, Weis, Joachim, additional, Van den Bergh, Peter, additional, Merrill, Shana, additional, Reilly, Mary, additional, Houlden, Henry, additional, Grossman, Murray, additional, Scherer, Steven, additional, De Jonghe, Peter, additional, Dyck, Peter, additional, and Klein, Christopher, additional

Published
2015
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15. CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures

Author

Thomas, Rhys H., primary, Zhang, Lin Mei, additional, Carvill, Gemma L., additional, Archer, John S., additional, Heavin, Sinéad B., additional, Mandelstam, Simone A., additional, Craiu, Dana, additional, Berkovic, Samuel F., additional, Gill, Deepak S., additional, Mefford, Heather C., additional, Scheffer, Ingrid E., additional, Paalotie, Aarno, additional, Lehesjoki, Anna-Elina, additional, Koeleman, Bobby, additional, Marini, Carla, additional, Depienne, Christel, additional, Pal, Deb, additional, Hoffman-Zacharska, Dorota, additional, Leguern, Eric, additional, Zara, Federico, additional, Rosenow, Felix, additional, Caglayan, Hande, additional, Hjalgrim, Helle, additional, Muhle, Hiltrud, additional, Lerche, Holger, additional, Helbig, Ingo, additional, Jähn, Johanna, additional, Lemke, Johannes, additional, Serratosa, Jose M, additional, Selmer, Kaja, additional, Klein, Karl Martin, additional, Sterbova, Katalin, additional, Pendziwiat, Manuela, additional, Barisic, Nina, additional, Gormley, Padhraig, additional, Striano, Pasquale, additional, May, Patrick, additional, De Jonghe, Peter, additional, Guerrini, Renzo, additional, Møller, Rikke, additional, Krause, Roland, additional, Balling, Rudi, additional, Sisodiya, Sanjay, additional, von Spiczak, Sarah, additional, Weckhuysen, Sarah, additional, Baulac, Stéphanie, additional, Suls, Arvid, additional, Djemie, Tania, additional, Talvik, Tiina, additional, Stephani, Ulrich, additional, Komarek, Vladimir, additional, and Weber, Yvonne, additional

Published
2015
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16. Absence epilepsies with widely variable onset are a key feature of autosomal dominant Glut1 deficiency

Author

Mullen, S.A., Suls, Arvid, Weber, Y., Lerche, H., De Jonghe, Peter, Berkovic, S.F., and Scheffer, I.E.

Subjects
Human medicine
Abstract

AB Background: Familial glucose transporter type 1 (GLUT1) deficiency due to autosomal dominant inheritance of SLC2A1 mutations is associated with paroxysmal exertional dyskinesia; epilepsy and intellectual disability occur in some family members. We recently demonstrated that GLUT1 deficiency occurs in over 10% of patients with early-onset absence epilepsy. Methods: This family study analyses the phenotypes in 2 kindreds segregating SLC2A1 mutations identified through probands with early-onset absence epilepsy. One comprised 9 individuals with mutations over 3 generations; the other had 6 individuals over 2 generations. Results: Of 15 subjects with SLC2A1 mutations, epilepsy occurred in 12. Absence seizures were the most prevalent seizure type (10/12), with onset from 3 to 34 years of age. Epilepsy phenotypes varied widely, including idiopathic generalized epilepsies (IGE) with absence (8/12), myoclonic-astatic epilepsy (2/12), and focal epilepsy (2/12). Paroxysmal exertional dyskinesia occurred in 7, and was subtle and universally undiagnosed prior to molecular diagnosis. There were 2 unaffected mutation carriers. Conclusions: GLUT1 deficiency is an important monogenic cause of absence epilepsies with onset from early childhood to adult life. Individual cases may be phenotypically indistinguishable from common forms of IGE. Although subtle paroxysmal exertional dyskinesia is a helpful diagnostic clue, it is far from universal. The phenotypic spectrum of GLUT1 deficiency is considerably greater than previously recognized. Diagnosis of GLUT1 deficiency has important treatment and genetic counseling implications.

Published
2010

18. Partial deletion of AFG3L2 causing spinocerebellar ataxia type 28

Author

Smets, Katrien, primary, Deconinck, Tine, additional, Baets, Jonathan, additional, Sieben, Anne, additional, Martin, Jean-Jacques, additional, Smouts, Iris, additional, Wang, Shuaiyu, additional, Taroni, Franco, additional, Di Bella, Daniela, additional, Van Hecke, Wim, additional, Parizel, Paul M., additional, Jadoul, Christina, additional, De Potter, Robert, additional, Couvreur, Francine, additional, Rugarli, Elena, additional, and De Jonghe, Peter, additional

Published
2014
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22. Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort.

Author

Gijselinck, Ilse, Van Mossevelde, Sara, van der Zee, Julie, Sieben, Anne, Philtjens, Stéphanie, Heeman, Bavo, Engelborghs, Sebastiaan, Vandenbulcke, Mathieu, De Baets, Greet, Bäumer, Veerle, Cuijt, Ivy, Van den Broeck, Marleen, Peeters, Karin, Mattheijssens, Maria, Rousseau, Frederic, Vandenberghe, Rik, De Jonghe, Peter, Cras, Patrick, De Deyn, Peter P., and Martin, Jean-Jacques

Published
2015
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24. DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy.

Author

Picard, Fabienne, Makrythanasis, Periklis, Navarro, Vincent, Ishida, Saeko, de Bellescize, Julitta, Ville, Dorothée, Weckhuysen, Sarah, Fosselle, Erwin, Suls, Arvid, De Jonghe, Peter, Vasselon Raina, Maryline, Lesca, Gaetan, Depienne, Christel, An-Gourfinkel, Isabelle, Vlaicu, Mihaela, Baulac, Michel, Mundwiller, Emeline, Couarch, Philippe, Combi, Romina, and Ferini-Strambi, Luigi

Published
2014
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27. STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.

Author

Stamberger H, Nikanorova M, Willemsen MH, Accorsi P, Angriman M, Baier H, Benkel-Herrenbrueck I, Benoit V, Budetta M, Caliebe A, Cantalupo G, Capovilla G, Casara G, Courage C, Deprez M, Destrée A, Dilena R, Erasmus CE, Fannemel M, Fjær R, Giordano L, Helbig KL, Heyne HO, Klepper J, Kluger GJ, Lederer D, Lodi M, Maier O, Merkenschlager A, Michelberger N, Minetti C, Muhle H, Phalin J, Ramsey K, Romeo A, Schallner J, Schanze I, Shinawi M, Sleegers K, Sterbova K, Syrbe S, Traverso M, Tzschach A, Uldall P, Van Coster R, Verhelst H, Viri M, Winter S, Wolff M, Zenker M, Zoccante L, De Jonghe P, Helbig I, Striano P, Lemke JR, Møller RS, and Weckhuysen S

Subjects
Adolescent, Adult, Brain Diseases diagnosis, Brain Diseases epidemiology, Child, Child, Preschool, Epilepsy diagnosis, Epilepsy epidemiology, Female, Humans, Infant, Male, Middle Aged, Mutation genetics, Neurodevelopmental Disorders diagnosis, Neurodevelopmental Disorders epidemiology, Young Adult, Brain Diseases genetics, Epilepsy genetics, Munc18 Proteins genetics, Neurodevelopmental Disorders genetics
Abstract

Objective: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients., Methods: We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients., Results: We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features., Conclusion: De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy., (© 2016 American Academy of Neurology.)

Published
2016
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28. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome.

Author

Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Møller RS, Hjalgrim H, Cook J, Geraghty E, O'Roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, von Spiczak S, Nikanorova M, Hodgson BL, Gazina EV, Suls A, Shendure J, Dibbens LM, De Jonghe P, Helbig I, Berkovic SF, Scheffer IE, and Mefford HC

Subjects
Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Nerve Tissue Proteins genetics, Young Adult, Epilepsies, Myoclonic genetics, Genetic Predisposition to Disease genetics, Munc18 Proteins genetics, Mutation genetics, Receptors, GABA-A genetics
Abstract

Objective: To determine the genes underlying Dravet syndrome in patients who do not have an SCN1A mutation on routine testing., Methods: We performed whole-exome sequencing in 13 SCN1A-negative patients with Dravet syndrome and targeted resequencing in 67 additional patients to identify new genes for this disorder., Results: We detected disease-causing mutations in 2 novel genes for Dravet syndrome, with mutations in GABRA1 in 4 cases and STXBP1 in 3. Furthermore, we identified 3 patients with previously undetected SCN1A mutations, suggesting that SCN1A mutations occur in even more than the currently accepted ∼ 75% of cases., Conclusions: We show that GABRA1 and STXBP1 make a significant contribution to Dravet syndrome after SCN1A abnormalities have been excluded. Our results have important implications for diagnostic testing, clinical management, and genetic counseling of patients with this devastating disorder and their families.

Published
2014
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29. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients.

Author

Weckhuysen S, Ivanovic V, Hendrickx R, Van Coster R, Hjalgrim H, Møller RS, Grønborg S, Schoonjans AS, Ceulemans B, Heavin SB, Eltze C, Horvath R, Casara G, Pisano T, Giordano L, Rostasy K, Haberlandt E, Albrecht B, Bevot A, Benkel I, Syrbe S, Sheidley B, Guerrini R, Poduri A, Lemke JR, Mandelstam S, Scheffer I, Angriman M, Striano P, Marini C, Suls A, and De Jonghe P

Subjects
Cohort Studies, DNA Mutational Analysis, Electroencephalography, Female, Humans, Infant, Male, Video Recording, Genetic Predisposition to Disease genetics, KCNQ2 Potassium Channel genetics, Mutation genetics, Spasms, Infantile genetics
Abstract

Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy., Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG., Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy., Conclusion: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible.

Published
2013
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31. Genetics of epilepsy syndromes starting in the first year of life.

Author

Deprez L, Jansen A, and De Jonghe P

Subjects
Humans, Infant, Infant, Newborn, Syndrome, Epilepsy genetics
Abstract

Background: Incidence rates of epilepsy in children are highest during the first year of life. Most frequently, epilepsy results from a metabolic or structural defect in the brain. However, some infants have clearly delineated epilepsy syndromes for which no underlying etiology can be identified except for a genetic predisposition., Methods: We reviewed the current knowledge on the genetics of epilepsy syndromes starting in the first year of life. We focus on those epilepsy syndromes without a clear structural or metabolic etiology., Results: Recent molecular studies have led to the identification of the responsible gene defects for several of the monogenetic epilepsy syndromes with onset in the first year of life., Discussion: This knowledge has consequences for clinical practice as it opens new perspectives for genetic testing, improving early diagnosis, and facilitating genetic counseling. This overview of epilepsy syndromes and associated gene defects might serve as a basis for the selection of patients in whom genetic testing can be helpful.

Published
2009
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