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

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
European Journal of Paediatric Neurology. 2020-09-01; 28: 214-220
DOI: 10.1016/J.EJPN.2020.06.002

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Cabasson S(1), Van-Gils J(2), Villéga F(3), Abi-Warde MT(4), Barcia G(5), Lazaro
L(6), Cancés C(7), Chelly J(8), Karsenty C(7), Rivera S(6), de Saint-Martin
A(4), Trimouille A(2), Villard L(9), Pédespan JM(3).

Author information:
(1)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:
.
(2)Service de génétique médicale. Centre Hospitalo-Universitaire de Bordeaux,
Hôpital Pellegrin Enfants, Place Amélie-Raba-Léon, 33 076, Bordeaux cedex,
France.
(3)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.
(4)Département de neurologie pédiatrique, CHRU de Strasbourg, 1 avenue Molière,
67 000, Strasbourg, France.
(5)Service de génétique médicale. Unité de génétique moléculaire, unité
d’embryologie moléculaire. Hôpital Necker-Enfants Malades, Tour Lavoisier
(3(ème) étage), 149 rue de Sèvres, 75743, Paris cedex 15, France.
(6)Service de pédiatrie. Centre hospitalier de la côte basque, 13 avenue de
l’interne Jacques-Loëb, 64 109, Bayonne, France.
(7)Service de Neuropédiatrie, Hôpital Purpan, 330 avenue de Grande-Bretagne,
31300, Toulouse, France.
(8)Unité de génétique moléculaire, Nouvel Hôpital Civil, 1 place de l’Hôpital,
BP 426, 67 091, Strasbourg cedex, France.
(9)Département de génétique médicale, Laboratoire de génétique moléculaire,
Assistance publique-Hôpitaux de Marseille, 264 rue Saint-Pierre, 13 385,
Marseille cedex 5, France.

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.