{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:45:03Z","timestamp":1790858703207,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T00:00:00Z","timestamp":1474848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,11]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>IQSEC<\/jats:styled-content>2<\/jats:italic> is an X\u2010linked gene associated with intellectual disability (ID<\/jats:styled-content>) and epilepsy. Herein we characterize the epilepsy\/epileptic encephalopathy of patients with IQSEC<\/jats:styled-content>2<\/jats:italic> pathogenic variants.<\/jats:p><\/jats:sec>Methods<\/jats:title>Forty\u2010eight patients with IQSEC<\/jats:styled-content>2<\/jats:italic> variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID<\/jats:styled-content> are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians.<\/jats:p><\/jats:sec>Results<\/jats:title>Six affected individuals had an inherited IQSEC<\/jats:styled-content>2<\/jats:italic> variant and 12 had a de novo one (male\u2010to\u2010female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic\u2013clonic (GTC<\/jats:styled-content>) seizures. The electroclinical syndromes could be defined in five patients: late\u2010onset epileptic spasms (three) and Lennox\u2010Gastaut or Lennox\u2010Gastaut\u2013like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC<\/jats:styled-content> and absence seizures in the hereditary cases and GTC<\/jats:styled-content> and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI<\/jats:styled-content>) were prominent features.<\/jats:p><\/jats:sec>Significance<\/jats:title>The phenotypic spectrum of IQSEC<\/jats:styled-content>2<\/jats:italic> disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC<\/jats:styled-content>2<\/jats:italic> should be evaluated in both male and female patients with an epileptic encephalopathy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13560","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T06:34:46Z","timestamp":1474871686000},"page":"1858-1869","source":"Crossref","is-referenced-by-count":58,"title":["The molecular and phenotypic spectrum of IQSEC<\/scp>2<\/i>\u2010related epilepsy"],"prefix":"10.1111","volume":"57","author":[{"given":"Ayelet","family":"Zerem","sequence":"first","affiliation":[{"name":"Pediatric Neurology Unit Metabolic\u2010Neurogenetic Clinic Wolfson Medical Center Institute of Medical Genetics Holon Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Haginoya","sequence":"additional","affiliation":[{"name":"Department of Neurology Takuto Rehabilitation Center for Children Miyagi Children's Hospital Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Lev","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Metabolic\u2010Neurogenetic Clinic Wolfson Medical Center Institute of Medical Genetics Holon Israel"},{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubov","family":"Blumkin","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Metabolic\u2010Neurogenetic Clinic Wolfson Medical Center Institute of Medical Genetics Holon Israel"},{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Kivity","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Metabolic\u2010Neurogenetic Clinic Wolfson Medical Center Institute of Medical Genetics Holon Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Linder","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Metabolic\u2010Neurogenetic Clinic Wolfson Medical Center Institute of Medical Genetics Holon Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Shoubridge","sequence":"additional","affiliation":[{"name":"Department of Paediatrics School of Paediatrics and Reproductive Health University of Adelaide Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Emma","family":"Palmer","sequence":"additional","affiliation":[{"name":"GOLD Genetics of Learning Disability Service Waratah New South Wales Australia"},{"name":"University of New South Wales Sydney New South Wales Australia"},{"name":"Department of Obstetrics and Gynecology The Prenatal Diagnosis and Medical Genetics Program Mount Sinai Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Field","sequence":"additional","affiliation":[{"name":"GOLD Genetics of Learning Disability Service Waratah New South Wales Australia"},{"name":"University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie","family":"Boyle","sequence":"additional","affiliation":[{"name":"GOLD Genetics of Learning Disability Service Waratah New South Wales Australia"},{"name":"University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chitayat","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Prenatal Diagnosis and Medical Genetics Program Mount Sinai Hospital University of Toronto Toronto Ontario Canada"},{"name":"Division of Clinical and Metabolic Genetics Department of Pediatrics The Hospital of Sickkids University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Gaillard","sequence":"additional","affiliation":[{"name":"Pediatrics and Neurology Division Epilepsy and Neurophysiology Comprehensive Pediatric Epilepsy Program Center for Neuroscience Research Children's National Medical Center George Washington University Washington District of Columbia U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Kossoff","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurology The Johns Hopkins Hospital Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolaine","family":"Willems","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Rare Diseases and Personalized Medicine Faculty of Medicine Unit INSERM 1183 CHU Montpellier University of Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Genevi\u00e8ve","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Rare Diseases and Personalized Medicine Faculty of Medicine Unit INSERM 1183 CHU Montpellier University of Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Tran\u2010Mau\u2010Them","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Rare Diseases and Personalized Medicine Faculty of Medicine Unit INSERM 1183 CHU Montpellier University of Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orna","family":"Epstein","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department Pediatric Epilepsy Service Asaf Harofeh Medical Center Zerifin Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Heyman","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department Pediatric Epilepsy Service Asaf Harofeh Medical Center Zerifin Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Dugan","sequence":"additional","affiliation":[{"name":"Children's Hospitals and Clinics of Minnesota Minneapolis Minnesota U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Masurel\u2010Paulet","sequence":"additional","affiliation":[{"name":"Reference Center for Developmental Anomalies and Syndromes Children's Hospital CHU Dijon Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ame'lie","family":"Piton","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics IGBMC CNRS UMR 7104\/INSERM U964\/Strasbourg University Strasbourg France"},{"name":"Genetic Diagnostic Laboratory University Hospitals of Strasbourg Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjitske","family":"Kleefstra","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud Institute for Molecular Life Sciences and Donders Centre for Neuroscience Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolph","family":"Pfundt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud Institute for Molecular Life Sciences and Donders Centre for Neuroscience Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Neurology Takuto Rehabilitation Center for Children Miyagi Children's Hospital Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Tzschach","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics University Hospital T\u00fcbingen T\u00fcbingen Germany"},{"name":"Institute of Clinical Genetics Technische Universit\u00e4t Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Saitsu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Leshinsky\u2010Silver","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Metabolic\u2010Neurogenetic Clinic Wolfson Medical Center Institute of Medical Genetics Holon Israel"},{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tally","family":"Lerman\u2010Sagie","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Metabolic\u2010Neurogenetic Clinic Wolfson Medical Center Institute of Medical Genetics Holon Israel"},{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,26]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"33","article-title":"Disruption of the IQSEC2 transcript in a female with X;autosome translocation t(X;20)(p11.2;q11.2) and a phenotype resembling X\u2010linked infantile spasms (ISSX) syndrome","volume":"1","author":"Morleo M","year":"2008","journal-title":"Mol Med 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