{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:11:36Z","timestamp":1792141896089,"version":"4.4.0"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Kleefstra syndrome (KS) or 9q34.3 microdeletion syndrome (OMIM #610253) is a rare genetic condition featuring intellectual disability, hypotonia, and dysmorphic facial features. Autism spectrum disorder, severe language impairment, and sleep disorders have also been described. The syndrome can be either caused by a microdeletion in 9q34.3 or by pathogenic variants in the euchromatin histone methyltransferase 1 gene (EHMT1, *607001). Although epilepsy has been reported in 20 to 30% of subjects, a detailed description of epileptic features and underlying etiology is still lacking. The purpose of this study is to investigate epilepsy features in a cohort of epileptic patients with KS.<\/jats:p><jats:p>\n          Methods\u2003This multicenter study investigated eight patients with KS and epilepsy. Our findings were compared with literature data.<\/jats:p><jats:p>\n          Results\u2003We included five patients with 9q or 9q34.33 deletions, a subject with a complex translocation involving EHMT1, and two with pathogenic EHMT1 variants. All patients presented with moderate to severe developmental delay, language impairment, microcephaly, and infantile hypotonia. Although the epileptic manifestations were heterogeneous, most patients experienced focal seizures. The seizure frequency differs according to the age of epilepsy onset, with patients with early-onset epilepsy (before 36 months of age) presenting more frequent seizures. An overtime reduction in seizure frequency, as well as in antiseizure drug number, was observed in all patients. Developmental delay degree did not correlate with seizure onset and frequency or drug resistance.<\/jats:p><jats:p>\n          Conclusion\u2003Epilepsy is a frequent finding in KS, but the underlying pathogenetic mechanism and specific features remain elusive.<\/jats:p>","DOI":"10.1055\/s-0043-1775977","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T22:50:32Z","timestamp":1696632632000},"page":"433-438","source":"Crossref","is-referenced-by-count":7,"title":["Electroclinical Features of Epilepsy in Kleefstra Syndrome"],"prefix":"10.1055","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7802-8789","authenticated-orcid":false,"given":"Thea","family":"Giacomini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy"},{"name":"Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7287-4159","authenticated-orcid":false,"given":"Ramona","family":"Cordani","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy"},{"name":"Unit of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Bagnasco","sequence":"additional","affiliation":[{"name":"Division of Child Neuropsychiatry, Martini Hospital, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6980-3248","authenticated-orcid":false,"given":"Fabiana","family":"Vercellino","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, SS Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Unit, Civilian Hospital, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Milito","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Unit, Civilian Hospital, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Battista","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, School of Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Mandrile","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, School of Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-7239","authenticated-orcid":false,"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaclaudia","family":"Meli","sequence":"additional","affiliation":[{"name":"Division of Paediatric Neurology, Department of Paediatrics, University of Catania, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Falsaperla","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, San Marco Hospital, University Hospital Policlinico \u201cG. Rodolico-San Marco,\u201d Catania, Italy"},{"name":"Unit of Pediatrics and Pediatric Emergency, University Hospital Policlinico \u201cG. Rodolico-San Marco,\u201d Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianvittorio","family":"Luria","sequence":"additional","affiliation":[{"name":"Department of Mathematics (DIMA), University of Genova, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"De Grandis","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy"},{"name":"Unit of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Canale","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Amadori","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Nobili","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy"},{"name":"Unit of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Siri","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1136\/jmg.2004.028464","article-title":"Disruption of the gene euchromatin histone methyl transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome","volume":"42","author":"T Kleefstra","year":"2005","journal-title":"J Med Genet"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1086\/505693","article-title":"Loss-of-function 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retardation","volume":"107","author":"B M Anderlid","year":"2002","journal-title":"Am J Med Genet"},{"issue":"06","key":"ref9","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/j.1399-0004.2002.tb02255.x","article-title":"Cryptic chromosome rearrangements detected by subtelomere assay in patients with mental retardation and dysmorphic features","volume":"62","author":"A J Dawson","year":"2002","journal-title":"Clin Genet"},{"issue":"08","key":"ref10","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1002\/ajmg.a.38852","article-title":"Pulmonary hypertension in patients with 9q34.3 microdeletion-associated Kleefstra syndrome","volume":"176","author":"V Okur","year":"2018","journal-title":"Am J Med Genet A"},{"issue":"10","key":"ref11","first-page":"650","article-title":"Kleefstra syndrome: the first case report from Iran","volume":"55","author":"M Noruzinia","year":"2017","journal-title":"Acta Med Iran"},{"issue":"01","key":"ref12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/ajmg.a.20457","article-title":"Submicroscopic deletion 9(q34.3) and duplication 19(p13.3): identified by subtelomere specific FISH probes","volume":"125A","author":"D I Quigley","year":"2004","journal-title":"Am J Med Genet A"},{"issue":"03","key":"ref13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/ajmg.a.20602","article-title":"9q34.3 deletion syndrome in three unrelated children","volume":"126A","author":"M Iwakoshi","year":"2004","journal-title":"Am J Med Genet A"},{"issue":"01","key":"ref14","doi-asserted-by":"crossref","first-page":"4928","DOI":"10.1038\/s41467-019-12947-3","article-title":"Neuronal network dysfunction in a model for Kleefstra syndrome mediated by enhanced NMDAR signaling","volume":"10","author":"M Frega","year":"2019","journal-title":"Nat Commun"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1399-0004.2010.01607.x","article-title":"Familial Kleefstra syndrome due to maternal somatic mosaicism for interstitial 9q34.3 microdeletions","volume":"80","author":"M H Willemsen","year":"2011","journal-title":"Clin 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