PURA-Related Developmental and Epileptic Encephalopathy Phenotypic and Genotypic Spectrum

Katrine M. Johannesen, Elena Gardella, Cathrine E. Gjerulfsen, Allan Bayat, Rob P.W. Rouhl, Margot Reijnders, Sandra Whalen, Boris Keren, Julien Buratti, Thomas Courtin, Klaas J. Wierenga, Bertrand Isidor, Amélie Piton, Laurence Faivre, Aurore Garde, Sébastien Moutton, Frédéric Tran-Mau-Them, Anne Sophie Denommé-Pichon, Christine Coubes, Austin LarsonMichael J. Esser, Juan Pablo Appendino, Walla Al-Hertani, Beatriz Gamboni, Alejandra Mampel, Lía Mayorga, Alessandro Orsini, Alice Bonuccelli, Agnese Suppiej, Julien Van-Gils, Julie Vogt, Simona Damioli, Lucio Giordano, Stephanie Moortgat, Elaine Wirrell, Sarah Hicks, Usha Kini, Nathan Noble, Helen Stewart, Shailesh Asakar, Julie S. Cohen, Sakku Bai R. Naidu, Ashley Collier, Eva H. Brilstra, Mindy H. Li, Casey Brew, Stefania Bigoni, Davide Ognibene, Elisa Ballardini, Claudia Ruivenkamp, Raffaella Faggioli, Alexandra Afenjar, Diana Rodriguez, David Bick, Devorah Segal, David Coman, Boudewijn Gunning, Orrin Devinsky, Laurie A. Demmer, Theresa Grebe, Dario Pruna, Ida Cursio, Lynn Greenhalgh, Claudio Graziano, Rahul Raman Singh, Gaetano Cantalupo, Marjolaine Willems, Sangeetha Yoganathan, Fernanda Góes, Richard J. Leventer, Davide Colavito, Sara Olivotto, Barbara Scelsa, Andrea V. Andrade, Kelly Ratke, Farha Tokarz, Atiya S. Khan, Clothilde Ormieres, William Benko, Karen Keough, Sotirios Keros, Shanawaz Hussain, Ashlea Franques, Felicia Varsalone, Sabine Grønborg, Cyril Mignot, Delphine Heron, Caroline Nava, Arnaud Isapof, Felippe Borlot, Robyn Whitney, Anne Ronan, Nicola Foulds, Marta Somorai, John Brandsema, Katherine L. Helbig, Ingo Helbig, Xilma R. Ortiz-González, Holly Dubbs, Antonio Vitobello, Mel Anderson, Dominic Spadafore, David Hunt, Rikke S. Møller, Guido Rubboli

Research output: Contribution to journalArticlepeer-review


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 Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature.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.

Original languageEnglish (US)
Article numbere613
JournalNeurology: Genetics
Issue number6
StatePublished - Dec 15 2021

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)


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