PURA-Related Developmental and Epileptic Encephalopathy

K.M. Johannesen*, E. Gardella, C.E. Gjerulfsen, A. Bayat, R.P.W. Rouhl, M. Reijnders, S. Whalen, B. Keren, J. Buratti, T. Courtin, K.J. Wierenga, B. Isidor, A. Piton, L. Faivre, A. Garde, S. Moutton, F. Tran-Mau-Them, A.S. Denomme-Pichon, C. Coubes, A. LarsonM.J. Esser, J.P. Appendino, W. Al-Hertani, B. Gamboni, A. Mampel, L. Mayorga, A. Orsini, A. Bonuccelli, A. Suppiej, J. Van-Gils, J. Vogt, S. Damioli, L. Giordano, S. Moortgat, E. Wirrell, S. Hicks, U. Kini, N. Noble, H. Stewart, S. Asakar, J.S. Cohen, S.R. Naidu, A. Collier, E.H. Brilstra, M.H. Li, C. Brew, S. Bigoni, D. Ognibene, E. Ballardini, C. Ruivenkamp, PURA study group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background and ObjectivesPurine-rich element-binding protein A (PURA) gene encodes Pur-alpha, 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spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients.MethodsData on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature.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.ResultsA 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.DiscussionThe 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
Article numbere613
Number of pages14
JournalNeurology. Genetics
Volume7
Issue number6
DOIs
Publication statusPublished - 1 Dec 2021

Keywords

  • POSTNATAL BRAIN-DEVELOPMENT
  • DE-NOVO MUTATIONS
  • CLASSIFICATION
  • PHENOTYPE
  • ALPHA
  • DELINEATION
  • EPILEPSIES
  • MORTALITY
  • FEATURES

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