PIGN encephalopathy: Characterizing the epileptology

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Allan Bayat - , University of Southern Denmark, Universität Kopenhagen (Autor:in)
  • Guillem de Valles-Ibáñez - , University of Otago (Autor:in)
  • Manuela Pendziwiat - , Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Alexej Knaus - , Universität Bonn (Autor:in)
  • Kerstin Alt - , Universitätsklinikum Ulm (Autor:in)
  • Elisa Biamino - , Ospedale Infantile Regina Margherita (Autor:in)
  • Annette Bley - , Universität Hamburg (Autor:in)
  • Sophie Calvert - , Children’s Health Queensland (Autor:in)
  • Patrick Carney - , University of Melbourne (Autor:in)
  • Alfonso Caro-Llopis - , Hospital Universitario La Fe (Autor:in)
  • Berten Ceulemans - , University of Antwerp (Autor:in)
  • Janice Cousin - , National Institutes of Health (NIH) (Autor:in)
  • Suzanne Davis - , University of Otago (Autor:in)
  • Vincent des Portes - , Hospices civils de Lyon (Autor:in)
  • Patrick Edery - , Hospices civils de Lyon (Autor:in)
  • Eleina England - , Massachusetts Institute of Technology (MIT) (Autor:in)
  • Carlos Ferreira - , National Institutes of Health (NIH) (Autor:in)
  • Jeremy Freeman - , Royal Children's Hospital Melbourne, Murdoch Children's Research Institute (Autor:in)
  • Blanca Gener - , Biocruces Bizkaia Instituto de Investigación Sanitaria (Autor:in)
  • Magali Gorce - , Université d'Angers (Autor:in)
  • Delphine Heron - , Sorbonne Université (Autor:in)
  • Michael S. Hildebrand - , Royal Children's Hospital Melbourne, University of Melbourne (Autor:in)
  • Aleksandra Jezela-Stanek - , National Institute of Tuberculosis and Lung Diseases (Autor:in)
  • Pierre Simon Jouk - , Université Grenoble Alpes (Autor:in)
  • Boris Keren - , Sorbonne Université (Autor:in)
  • Katja Kloth - , Universität Hamburg (Autor:in)
  • Gerhard Kluger - , Universitätsklinikum Ulm (Autor:in)
  • Marius Kuhn - , Universitätsklinikum Ulm (Autor:in)
  • Johannes R. Lemke - , Universität Leipzig (Autor:in)
  • Hong Li - , Emory University (Autor:in)
  • Francisco Martinez - , Hospital Universitario La Fe (Autor:in)
  • Caroline Maxton - , Zentrum für Kinderneurologie (Autor:in)
  • Heather C. Mefford - , St. Jude Children Research Hospital (Autor:in)
  • Giuseppe Merla - , Ospedale Infantile Regina Margherita (Autor:in)
  • Hanna Mierzewska - , Institute of Mother and Child (Autor:in)
  • Alison Muir - , St. Jude Children Research Hospital (Autor:in)
  • Sandra Monfort - , Maastricht University (Autor:in)
  • Joost Nicolai - , Maastricht University (Autor:in)
  • Jennifer Norman - , INTEGRIS Pediatric Neurology (Autor:in)
  • Gina O'Grady - , Auckland District Health Board (Autor:in)
  • Barbara Oleksy - , Universität Heidelberg (Autor:in)
  • Carmen Orellana - , Maastricht University (Autor:in)
  • Laura Elena Orec - , Children's Memorial Health Institute (Autor:in)
  • Charlotte Peinhardt - , Emory University (Autor:in)
  • Ewa Pronicka - , Universidad Autónoma de Madrid (Autor:in)
  • Monica Rosello - , Maastricht University (Autor:in)
  • Fernando Santos-Simarro - , Universität Heidelberg (Autor:in)
  • Eva Maria Christina Schwaibold - , Maastricht University (Autor:in)
  • Alexander P.A. Stegmann - , Maastricht University (Autor:in)
  • Constance T Stumpel - , Université Bourgogne Franche-Comté (Autor:in)
  • Elzbieta Szczepanik - , Universität Heidelberg (Autor:in)
  • Iwona Terczyńska - , Technische Universität Dresden (Autor:in)
  • Julien Thevenon - , University of Antwerp (Autor:in)
  • Andreas Tzschach - , University of Antwerp (Autor:in)
  • Patrick Van Bogaert - , Université d'Angers (Autor:in)
  • Roberta Vittorini - , Ospedale Infantile Regina Margherita (Autor:in)
  • Sonja Walsh - , Klinik und Poliklinik für Kinder- und Jugendmedizin, Abteilung für Neuropädiatrie (Autor:in)
  • Sarah Weckhuysen - , Université de Lausanne, Harvard University (Autor:in)
  • Barbara Weissman - , Children's Memorial Health Institute (Autor:in)
  • Lynne Wolfe - , National Institutes of Health (NIH) (Autor:in)
  • Alexandre Reymond - , IRCCS Istituto Giannina Gaslini - Genova (Autor:in)
  • Pasquelena De Nittis - , IRCCS Istituto Giannina Gaslini - Genova (Autor:in)
  • Annapurna Poduri - , University of Melbourne (Autor:in)
  • Heather Olson - , University of Melbourne (Autor:in)
  • Pasquale Striano - , IRCCS Istituto Giannina Gaslini - Genova (Autor:in)
  • Gaetan Lesca - , Hospices civils de Lyon (Autor:in)
  • Ingrid E. Scheffer - , Royal Children's Hospital Melbourne, University of Melbourne (Autor:in)
  • Rikke S. Møller - , University of Southern Denmark, Universität Kopenhagen (Autor:in)
  • Lynette G. Sadleir - , University of Otago (Autor:in)

Abstract

Objective: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. Methods: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. Results: Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic–atonic (1/26), and generalized tonic–clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. Significance: PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment.

Details

OriginalspracheEnglisch
Seiten (von - bis)974-991
Seitenumfang18
FachzeitschriftEpilepsia
Jahrgang63
Ausgabenummer4
PublikationsstatusVeröffentlicht - Apr. 2022
Peer-Review-StatusJa

Externe IDs

PubMed 35179230

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • congenital disorder of glycosylation, developmental and epileptic encephalopathy, epilepsy, GPI-anchoring disorder, intellectual disability

Bibliotheksschlagworte