PIGN encephalopathy: Characterizing the epileptology.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Bayat A
  • de Valles-Ibáñez G
  • Pendziwiat M
  • Knaus A
  • Alt K
  • Biamino E
  • Bley A
  • Calvert S
  • Carney P
  • Ceulemans B
  • Cousin J
  • Davis S
  • des Portes V
  • Edery P
  • England E
  • Ferreira C
  • Freeman J
  • Gener B
  • Gorce M
  • Heron D
  • Hildebrand MS
  • Jezela-Stanek A
  • Jouk PS
  • Keren B
  • Kloth K
  • Kluger G
  • Kuhn M
  • Lemke JR
  • Li H
  • Maxton C
  • Mefford HC
  • Merla G
  • Mierzewska H
  • Muir A
  • Monfort S
  • Nicolai J
  • Norman J
  • O'Grady G
  • Oleksy B
  • Orellana C
  • Orec LE
  • Peinhardt C
  • Pronicka E
  • Rosello M
  • Santos-Simarro F
  • Schwaibold EMC
  • Stegmann APA
  • Stumpel CT
  • Szczepanik E
  • Terczynska I
  • Thevenon J
  • Tzschach A
  • Van Bogaert P
  • Vittorini R
  • Walsh S
  • Weckhuysen S
  • Weissman B
  • Wolfe L
  • Reymond A
  • De Nittis P
  • Poduri A
  • Olson H
  • Striano P
  • Lesca G
  • Scheffer IE
  • Møller RS
  • Sadleir LG

Grupos

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.

© 2022 International League Against Epilepsy.

Datos de la publicación

ISSN/ISSNe:
0013-9580, 1528-1167

Epilepsia  WILEY

Tipo:
Article
Páginas:
974-991
Factor de Impacto:
1,893 SCImago
Cuartil:
Q1 SCImago

Citas Recibidas en Web of Science: 3

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

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

Campos de estudio

Proyectos asociados

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

COMPREHENSIVE, INTEGRATIVE AND GENOMIC APPROACH TO THE UNDERSTANDING AND TREATMENT OF CANCER AND LEUKEMIA.

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

PIE13/00046 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014

LA RUTA DE LA OXITOCINA EN LOS TRASTORNOS DEL ESPECTRO AUTISTA: IMPORTANCIA DE LAS VARIANTES GENÉTICAS CON RELEVANCIA FUNCIONAL.

Investigador Principal: CARMEN ORELLANA ALONSO

2014_0056_CRC_ORELLANA . 2014

ABORDAJE GENÓMICO PARA LA IDENTIFICACIÓN DE NUEVOS GENES Y MÓDULOS FUNCIONALES RESPONSABLES DE DISCAPACIDAD INTELECTUAL GRAVE.

Investigador Principal: FRANCISCO MARTÍNEZ CASTELLANO

PI14/00350 . INSTITUTO DE SALUD CARLOS III . 2015

NUEVA APROXIMACIÓN GENÓMICA PARA EL DIAGNÓSTICO DE AUTISMO Y DISCAPACIDAD INTELECTUAL: IMPORTANCIA DE LAS MUTACIONES ADQUIRIDAS EN MOSAICISMO SOMÁTICO Y DE NUEVOS GENES CANDIDATOS.

Investigador Principal: SANDRA MONFORT MEMBRADO

2018_0170_CRC_MUTUA MADRILEÑA_MONFORT . FUNDACION MUTUA MADRILEÑA . 2018

Contrato Post FSE (Rio Hortega).

Investigador Principal: FRANCISCO MARTÍNEZ CASTELLANO

CM19/00181 . INSTITUTO DE SALUD CARLOS III . 2020

Cita

Compartir