Correlation Engine 2.0
Clear Search sequence regions

The molecular diagnosis of early-onset epileptic encephalopathy (EOEE), an expanding field in child neurology, is becoming increasingly possible thanks to the widespread availability of next-generation sequencing and whole-exome sequencing. In the past 15 years, mutations in STXBP1, KCNQ2, SCN2A, SCN8A and numerous other genes have been reported, giving a more accurate insight for these rare diseases. Among these genes, germline mutations in Phosphatidyl Inositol Glycan A (PIGA) gene were first reported in 2012. Located on Xp22.2, PIGA is involved in the synthesis of GPI (glycosylphosphatidylinositol) which acts as a membrane anchor for different proteins: enzymes, adhesion molecules, regulation of the complement way, and co-receptor in transduction signal. Children suffering from this condition exhibit developmental delay with early-onset epilepsy, severe dysmorphic signs, multi-visceral anomalies and early death in the most severe forms. Here, we report five cases of germline PIGA mutations, with two missense mutations that have not been reported to date. We provide a new insight into the electroclinical phenotype. At the onset, epileptic spasms and focal-onset seizures with upper limbs and ocular involvements were present. Epilepsy proved pharmacoresistant in 4 out of 5 cases. Interictal EEG may be normal at the onset of epilepsy, but abnormalities in electroencephalographic studies were eventually present in all cases. Different types of seizures may be present simultaneously, and epileptic phenotypes evolve with aging. Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.


Sébastien Cabasson, Julien Van-Gils, Frédéric Villéga, Marie-Thérèse Abi-Warde, Giulia Barcia, Leila Lazaro, Claude Cancés, Jamel Chelly, Caroline Karsenty, Serge Rivera, Anne de Saint-Martin, Aurélien Trimouille, Laurent Villard, Jean-Michel Pédespan. Early-onset epileptic encephalopathy related to germline PIGA mutations: A series of 5 cases. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2020 Sep;28:214-220

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 32694024

View Full Text