TY - JOUR
T1 - PURA-Related Developmental and Epileptic Encephalopathy
T2 - Phenotypic and Genotypic Spectrum
AU - Johannesen, Katrine M.
AU - Gardella, Elena
AU - Gjerulfsen, Cathrine E.
AU - Bayat, Allan
AU - Rouhl, Rob P.W.
AU - Reijnders, Margot
AU - Whalen, Sandra
AU - Keren, Boris
AU - Buratti, Julien
AU - Courtin, Thomas
AU - Wierenga, Klaas J.
AU - Isidor, Bertrand
AU - Piton, Amélie
AU - Faivre, Laurence
AU - Garde, Aurore
AU - Moutton, Sébastien
AU - Tran-Mau-Them, Frédéric
AU - Denommé-Pichon, Anne Sophie
AU - Coubes, Christine
AU - Larson, Austin
AU - Esser, Michael J.
AU - Appendino, Juan Pablo
AU - Al-Hertani, Walla
AU - Gamboni, Beatriz
AU - Mampel, Alejandra
AU - Mayorga, Lía
AU - Orsini, Alessandro
AU - Bonuccelli, Alice
AU - Suppiej, Agnese
AU - Van-Gils, Julien
AU - Vogt, Julie
AU - Damioli, Simona
AU - Giordano, Lucio
AU - Moortgat, Stephanie
AU - Wirrell, Elaine
AU - Hicks, Sarah
AU - Kini, Usha
AU - Noble, Nathan
AU - Stewart, Helen
AU - Asakar, Shailesh
AU - Cohen, Julie S.
AU - Naidu, Sakku Bai R.
AU - Collier, Ashley
AU - Brilstra, Eva H.
AU - Li, Mindy H.
AU - Brew, Casey
AU - Bigoni, Stefania
AU - Ognibene, Davide
AU - Møller, Rikke S.
AU - Rubboli, Guido
AU - PURA study group
N1 - Funding Information:
The authors are deeply grateful for the collaboration and support from all the PURA families, and the authors wish to acknowledge the PURA foundation for their tireless work and commitment to advance the knowledge on PURA syndrome. The authors thank Diana Baralle for inclusion of patients and Dierk Niessing and Robert Janowski for their invaluable support and comments on the manuscript. The authors thank the following for their contributions to the study: Deborah Mitchell-Langlois. The authors thank Jean-François Deleuze, Anne Boland-Augé, and Robert Olaso for the collaboration CEA/JACOB/CNRGH—CHU de Dijon—Inserm.
Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.
AB - Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.
U2 - 10.1212/NXG.0000000000000613
DO - 10.1212/NXG.0000000000000613
M3 - Journal article
C2 - 34790866
AN - SCOPUS:85121913018
SN - 2376-7839
VL - 7
JO - Neurology: Genetics
JF - Neurology: Genetics
IS - 6
M1 - e613
ER -