Developmental epileptic encephalopathy in <i>DLG4</i>‐related synaptopathy

  1. Kassabian, Benedetta 1362
  2. Levy, Amanda M. 20
  3. Gardella, Elena 1314
  4. Aledo‐Serrano, Angel 44
  5. Ananth, Amitha L. 26
  6. Brea‐Fernández, Alejandro J. 910
  7. Caumes, Roseline 66
  8. Chatron, Nicolas 2829
  9. Dainelli, Alice 19
  10. De Wachter, Matthias 8
  11. Denommé‐Pichon, Anne‐Sophie 3738
  12. Dye, Thomas J. 3334
  13. Fazzi, Elisa 3031
  14. Felt, Roxanne 36
  15. Fernández‐Jaén, Alberto 1516
  16. Fernández‐Prieto, Montserrat 910
  17. Gantz, Emily 26
  18. Gasperowicz, Piotr 47
  19. Gil‐Nagel, Antonio 39
  20. Gómez‐Andrés, David 45
  21. Greiner, Hansel M. 3334
  22. Guerrini, Renzo 19
  23. Haanpää, Maria K. 55
  24. Helin, Minttu 18
  25. Hoyer, Juliane 6
  26. Hurst, Anna C. E. 50
  27. Kallish, Staci 68
  28. Karkare, Shefali N. 17
  29. Khan, Amjad 5960
  30. Kleinendorst, Lotte 1112
  31. Koch, Johannes 56
  32. Kothare, Sanjeev V. 17
  33. Koudijs, Suzanna V. 34
  34. Lagae, Lieven 32
  35. Lakeman, Phillis 11
  36. Leppig, Kathleen A. 52
  37. Lesca, Gaetan 2829
  38. Lopergolo, Diego 524
  39. Lusk, Laina 40
  40. Mackenzie, Alex 5354
  41. Mei, Davide 19
  42. Møller, Rikke S. 1314
  43. Pereira, Elaine M. 41
  44. Platzer, Konrad 27
  45. Quelin, Chloe 35
  46. Revah‐Politi, Anya 42
  47. Rheims, Sylvain 63
  48. Rodríguez‐Palmero, Agustí 5758
  49. Rossi, Andrea 31
  50. Santorelli, Filippo 5
  51. Seinfeld, Syndi 21
  52. Sell, Erick 61
  53. Stephenson, Donna 43
  54. Szczaluba, Krzysztof 4767
  55. Trinka, Eugen 4849
  56. Umair, Muhammad 6465
  57. Van Esch, Hilde 7
  58. van Haelst, Mieke M. 1112
  59. Veenma, Danielle C. M. 451
  60. Weber, Sacha 2223
  61. Weckhuysen, Sarah 12
  62. Zacher, Pia 46
  63. Tümer, Zeynep 2025
  64. Rubboli, Guido 1325
  65. Mostrar todos los/as autores/as +
  1. 1 Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB Antwerp Belgium
  2. 2 Department of Neurology Antwerp University Hospital Antwerp Belgium
  3. 3 Erasmus MC Sophia Children's Hospital, Department of Neurology Rotterdam The Netherlands
  4. 4 ENCORE‐GRIN Expertise Center Rotterdam Netherlands
  5. 5 IRCCS Stella Maris Foundation, Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit Pisa Italy
  6. 6 Friedrich‐Alexander‐Universität Erlangen Nürnberg (FAU) Institute of Human Genetics Erlangen Germany
  7. 7 Center for Human Genetics University Hospitals Leuven Leuven Belgium
  8. 8 Department of Pediatric Neurology, Antwerp University Hospital University of Antwerp Edegem Belgium
  9. 9 Grupo de Genómica y Bioinformática, CIMUS, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER‐ISCIII), Universidade de Santiago de Compostela Santiago de Compostela Spain
  10. 10 Grupo de Genética, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Biomédica de Santiago (IDIS), Santiago de Compostela Spain
  11. 11 Department of Human Genetics, Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
  12. 12 Emma Center for Personalized Medicine, Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
  13. 13 Department of Epilepsy Genetics and Precision Medicine, Danish Epilepsy Center Filadelfia Dianalund Denmark
  14. 14 Department of Regional Health Research University of Southern Denmark Odense Denmark
  15. 15 Department of Pediatric Neurology, Neurogenetics Section, Hospital Universitario Quirónsalud Madrid Spain
  16. 16 Facultad de Medicina, Universidad Europea Madrid Spain
  17. 17 Division of Pediatric Neurology, Department of Pediatrics, Cohen Children's Medical Center New Hyde Park NY USA
  18. 18 Department of Pediatric Neurology Turku University Hospital Turku Finland
  19. 19 Neuroscience Department, Meyer Children's Hospital IRCCS Florence Italy
  20. 20 Department of Clinical Genetics, Kennedy Center Copenhagen University Hospital Rigshospitalet Copenhagen Denmark
  21. 21 Joe DiMaggio Children's Hospital Hollywood FL USA
  22. 22 Service de Génétique CHU de Caen‐Normandie Caen France
  23. 23 Service de Neurologie CHU de Caen‐Normandie Caen France
  24. 24 Department of Medicine, Surgery and Neurosciences University of Siena Siena Italy
  25. 25 Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark
  26. 26 Division of Pediatric Neurology University of Alabama at Birmingham Birmingham AL USA
  27. 27 Institute of Human Genetics University of Leipzig Medical Center Leipzig Germany
  28. 28 Service de Genetique Hospices Civils de Lyon Bron France
  29. 29 Institute NeuroMyoGène, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, CNRS UMR 5261 ‐ INSERM U1315 Université de Lyon ‐ Université Claude Bernard Lyon 1 Lyon France
  30. 30 Department of Clinical and Experimental Sciences University of Brescia Brescia Italy
  31. 31 Unit of Child Neurology and Psychiatry, ASST Spedali Civili of Brescia Brescia Italy
  32. 32 University Hospitals Leuven Department Development and Regeneration, Section Paediatric Neurology Leuven Belgium
  33. 33 Cincinnati Children's Hospital Medical Center, Division of Neurology Cincinnati OH USA
  34. 34 University of Cincinnati College of Medicine Department of Pediatrics Cincinnati OH USA
  35. 35 Department of Medical Genetics, CHU de Rennes Rennes France
  36. 36 Department of Neurology, Kaiser Permanente Bellevue Medical Center Bellevue WA USA
  37. 37 Functional Unit for Diagnostic Innovation in Rare Diseases, FHU‐TRANSLAD Dijon Bourgogne University Hospital Dijon France
  38. 38 INSERM UMR1231 GAD "Génétique des Anomalies du Développement" FHU‐TRANSLAD University of Burgundy Dijon France
  39. 39 Epilepsy Program, Neurology Department, Ruber Internacional Hospital Madrid Spain
  40. 40 Epilepsy Neurogenetics Initiative (ENGIN), Division of Neurology, Children's Hospital of Philadelphia Philadelphia PA USA
  41. 41 Division of Clinical Genetics, Department of Pediatrics Columbia University Vagelos College of Physicians and Surgeons and NewYork‐Presbyterian Morgan Stanley Children's Hospital New York NY USA
  42. 42 Institute for Genomic Medicine Columbia University Irving Medical Center New York NY USA
  43. 43 Division of Neurology, Children's Hospital of Philadelphia Philadelphia PA USA
  44. 44 Epilepsy and Neurogenetics Unit, Vithas La Milagrosa University Hospital Vithas Hospital Group Madrid Spain
  45. 45 Child Neurology Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona Spain
  46. 46 Epilepsy Center Kleinwachau Radeberg Germany
  47. 47 Department of Medical Genetics Medical University of Warsaw Warsaw Poland
  48. 48 Department of Neurology, Neurointensive Care and Neurorehabilitation Christian Doppler University Hospital Paracelsus Medical University, Centre for Cognitive Neuroscience Salzburg Austria
  49. 49 Neuroscience Institute Christian Doppler University Hospital, Paracelsus Medical University, Centre for Cognitive Neuroscience Salzburg Austria
  50. 50 Department of Genetics University of Alabama at Birmingham Birmingham AL USA
  51. 51 General Pediatrics Department, Erasmus MC‐Sophia Hospital, Rotterdam The Hague The Netherlands
  52. 52 Genetic Services, Kaiser Permanente of Washington Seattle WA USA
  53. 53 Research Institute Children's Hospital of Eastern Ontario Ottawa ON Canada
  54. 54 Faculty of Medicine University of Ottawa Ottawa ON Canada
  55. 55 Department of Genomics Turku University Hospital Turku Finland
  56. 56 University Children's Hospital Paracelsus Medical University Salzburg Austria
  57. 57 Paediatric Neurology Unit, Department of Pediatrics, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona Barcelona Spain
  58. 58 CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII Madrid Spain
  59. 59 Institute for Medical Genetics and Applied Genomics University of Tübingen Tübingen Germany
  60. 60 Alexander von Humboldt Fellowship Foundation Berlin Germany
  61. 61 Division of Neurology, Children's Hospital of Eastern Ontario Ottawa ON Canada
  62. 62 Neurology Unit, Department of Neurosciences University of Padua Padua Italy
  63. 63 Department of Functional Neurology and Epileptology Hospices Civils de Lyon and Lyon 1 University Lyon France
  64. 64 Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC) King Saud Bin Abdulaziz University for Health Sciences Ministry of National Guard Health Affairs (MNGH), Riyadh Saudi Arabia
  65. 65 Department of Life Sciences, School of Science University of Management and Technology Lahore Pakistan
  66. 66 CHU de Lille, Clinique de Génétique Lille France
  67. 67 Centre of Excellence for Rare and Undiagnosed Diseases of the Medical University of Warsaw Warsaw Poland
  68. 68 Department of Medicine, Division of Translational Medicine and Human Genetics University of Pennsylvania Philadelphia PA USA
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Revista:
Epilepsia

ISSN: 0013-9580,  1528-1167

Año de publicación: 2023

Tipo: Artículo

DOI: 10.1111/EPI.17876 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Epilepsia

Objetivos de desarrollo sostenible

Resumen

ObjectiveThe postsynaptic density protein of excitatory neurons PSD-95 is encoded by DLG4, de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy.MethodsWe included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep EEG and/or video-polygraphy and brain MRI were collected. Anti-seizure medication response was retrospectively assessed by the referring clinician.ResultsA large variety of seizure types was reported, though focal seizures were the most common. Encephalopathy related to status epilepticus during slow sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in more than 25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants.SignificanceOur study shows that a subgroup of individuals with DLG4-related synaptopathy has DEE, and around one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires to be properly investigated with sleep EEG.

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