Early-onset epileptic encephalopathy related to germline PIGA mutations: A series of 5 cases. 2020

Sébastien Cabasson, and Julien Van-Gils, and Frédéric Villéga, and Marie-Thérèse Abi-Warde, and Giulia Barcia, and Leila Lazaro, and Claude Cancés, and Jamel Chelly, and Caroline Karsenty, and Serge Rivera, and Anne de Saint-Martin, and Aurélien Trimouille, and Laurent Villard, and Jean-Michel Pédespan
Unité de neurologie de l'enfant et de l'adolescent. Centre Hospitalo-Universitaire de Bordeaux, Hôpital Pellegrin Enfants, Place Amélie-Raba-Léon, 33 076, Bordeaux cedex, France. Electronic address: sebastiencabasson@yahoo.fr.

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.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D008297 Male Males
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013036 Spasms, Infantile An epileptic syndrome characterized by the triad of infantile spasms, hypsarrhythmia, and arrest of psychomotor development at seizure onset. The majority present between 3-12 months of age, with spasms consisting of combinations of brief flexor or extensor movements of the head, trunk, and limbs. The condition is divided into two forms: cryptogenic (idiopathic) and symptomatic (secondary to a known disease process such as intrauterine infections; nervous system abnormalities; BRAIN DISEASES, METABOLIC, INBORN; prematurity; perinatal asphyxia; TUBEROUS SCLEROSIS; etc.). (From Menkes, Textbook of Child Neurology, 5th ed, pp744-8) Cryptogenic Infantile Spasms,Hypsarrhythmia,Infantile Spasms,Jackknife Seizures,Nodding Spasm,Salaam Seizures,Spasmus Nutans,Symptomatic Infantile Spasms,West Syndrome,Cryptogenic West Syndrome,Lightning Attacks,Salaam Attacks,Symptomatic West Syndrome,Attack, Lightning,Attacks, Lightning,Attacks, Salaam,Cryptogenic Infantile Spasm,Hypsarrhythmias,Infantile Spasm,Infantile Spasm, Cryptogenic,Infantile Spasm, Symptomatic,Infantile Spasms, Cryptogenic,Infantile Spasms, Symptomatic,Jackknife Seizure,Lightning Attack,Nodding Spasms,Seizure, Jackknife,Seizures, Jackknife,Seizures, Salaam,Spasm, Cryptogenic Infantile,Spasm, Nodding,Spasm, Symptomatic Infantile,Spasms, Cryptogenic Infantile,Spasms, Nodding,Spasms, Symptomatic Infantile,Symptomatic Infantile Spasm,Syndrome, Cryptogenic West,Syndrome, Symptomatic West,Syndrome, West,West Syndrome, Cryptogenic,West Syndrome, Symptomatic
D059014 High-Throughput Nucleotide Sequencing Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc. High-Throughput Sequencing,Illumina Sequencing,Ion Proton Sequencing,Ion Torrent Sequencing,Next-Generation Sequencing,Deep Sequencing,High-Throughput DNA Sequencing,High-Throughput RNA Sequencing,Massively-Parallel Sequencing,Pyrosequencing,DNA Sequencing, High-Throughput,High Throughput DNA Sequencing,High Throughput Nucleotide Sequencing,High Throughput RNA Sequencing,High Throughput Sequencing,Massively Parallel Sequencing,Next Generation Sequencing,Nucleotide Sequencing, High-Throughput,RNA Sequencing, High-Throughput,Sequencing, Deep,Sequencing, High-Throughput,Sequencing, High-Throughput DNA,Sequencing, High-Throughput Nucleotide,Sequencing, High-Throughput RNA,Sequencing, Illumina,Sequencing, Ion Proton,Sequencing, Ion Torrent,Sequencing, Massively-Parallel,Sequencing, Next-Generation

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