6533b82cfe1ef96bd128f4d2
RESEARCH PRODUCT
PURA- Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum
Dario PrunaTheresa GrebeFelippe BorlotMichael J. EsserJuan Pablo AppendinoKatherine L. HelbigElisa BallardiniCasey BrewAnne-sophie Denommé-pichonAnne RonanLaurie A. DemmerUsha KiniMarta SomoraiJulie VogtSébastien MouttonRaffaella FaggioliJulien Van-gilsDavide OgnibeneSara OlivottoSabine GrønborgDavid ComanDavid P. BickGuido RubboliOrrin DevinskyAtiya S. KhanRobyn WhitneyChristine CoubesCaroline NavaKaren KeoughSakkubai R. NaiduLucio GiordanoDavide ColavitoDominic SpadaforeArnaud IsapofWalla Al-hertaniAntonio VitobelloAndrea V. AndradeGaetano CantalupoSandra WhalenBoudewijn GunningShanawaz HussainDavid HuntNathan NobleBertrand IsidorBeatriz GamboniKatrine M JohannesenJulien BurattiStephanie MoortgatIda CursioAgnese SuppiejDelphine HéronLía MayorgaWilliam BenkoRahul Raman SinghCyril MignotSotirios KerosAurore GardeNicola FouldsClaudia A. L. RuivenkampElena GardellaBarbara ScelsaFernanda GóesLaurence FaivreRichard J. LeventerAshley CollierFarha TokarzThomas CourtinKlaas J. WierengaXilma R. Ortiz-gonzalezFrédéric Tran-mau-themAlejandra MampelLynn GreenhalghAshlea FranquesAmélie PitonFelicia VarsaloneMarjolaine WillemsAlessandro OrsiniDiana RodriguezClothilde OrmieresHelen StewartBoris KerenAustin LarsonCathrine E. GjerulfsenJulie S. CohenMargot R.f. ReijndersMel AndersonShailesh AsakarRikke Rs MøllerAlice BonuccelliAlexandra AfenjarClaudio GrazianoElaine WirrellSimona DamioliSangeetha YoganathanDevorah SegalIngo HelbigMindy H. LiRob P.w. RouhlSarah HicksAllan BayatHolly DubbsStefania BigoniKelly RatkeJohn BrandsemaEva H. Brilstrasubject
Pediatricsmedicine.medical_specialtySocio-culturale[SDV.GEN] Life Sciences [q-bio]/GeneticsElectroencephalographyEpilepsyDevelopmental and Epileptic EncephalopathyIntellectual disabilitymedicineGenetics (clinical)feeding difficulties[SDV.GEN]Life Sciences [q-bio]/Geneticsmedicine.diagnostic_testbusiness.industryfungimedicine.diseaseHypotoniaEpileptic spasmsNeonatal hypotonianeonatal hypotoniaEpilepsy syndromesCohortepilepsyNeurology (clinical)medicine.symptombusinessdescription
Background and ObjectivesPurine-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.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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-12-15 |