{"entity": "journal", "iuid": "445edbd0308c4c718f37fc33a5087e46", "timestamp": "2026-07-20T21:35:33.237Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Epilepsia.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Epilepsia"}}, "title": "Epilepsia", "issn": "1528-1167", "issn-l": "0013-9580", "publications_count": 3, "publications": [{"entity": "publication", "iuid": "508dbf0c7a8540809bc38d4710d43948", "links": {"self": {"href": "https://publications.scilifelab.se/publication/508dbf0c7a8540809bc38d4710d43948.json"}, "display": {"href": "https://publications.scilifelab.se/publication/508dbf0c7a8540809bc38d4710d43948"}}, "title": "Clinical whole genome sequencing in pediatric epilepsy: Genetic and phenotypic spectrum of 733 individuals.", "authors": [{"family": "Henry", "given": "Olivia J", "initials": "OJ", "orcid": "0000-0002-4717-8346", "researcher": {"href": "https://publications.scilifelab.se/researcher/1226db94b02c4ceda75fd5903c4815a0.json"}}, {"family": "Ygberg", "given": "Sofia", "initials": "S"}, {"family": "Barbaro", "given": "Michela", "initials": "M"}, {"family": "Lesko", "given": "Nicole", "initials": "N"}, {"family": "Karlsson", "given": "Leif", "initials": "L", "orcid": "0000-0001-6274-9330", "researcher": {"href": "https://publications.scilifelab.se/researcher/5a90f592b91c4f3b9568cb086f568a98.json"}}, {"family": "Pe\u00f1a-P\u00e9rez", "given": "Luc\u00eda", "initials": "L"}, {"family": "B\u00e5vner", "given": "Ann", "initials": "A"}, {"family": "T\u00f6h\u00f6nen", "given": "Virpi", "initials": "V"}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "St\u00f6dberg", "given": "Tommy", "initials": "T"}, {"family": "Wedell", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2025-08-00", "journal": {"title": "Epilepsia", "issn": "1528-1167", "volume": "66", "issue": "8", "pages": "2966-2979", "issn-l": "0013-9580"}, "abstract": "A large proportion of pediatric epilepsies have an underlying genetic etiology. Limited studies have explored the efficacy of whole genome sequencing (WGS) in a clinical setting. Our academic-clinical center implemented clinical whole exome sequencing (WES) in 2014, then transitioned to WGS from 2015. We report the diagnostic yield, genetic and phenotypic findings, and prognostic factors following WGS/WES in pediatric epilepsy.\n\nThe cohort included 733 families with pediatric epilepsy who received clinical WGS/WES between 2014 and 2022. WGS/WES was performed at the Genomic Medicine Center Karolinska for Rare Diseases and analyzed at the Center for Inherited Metabolic Diseases at Karolinska University Hospital. Phenotypic information was extracted from referrals and medical records. Genetic and phenotypic data were analyzed using descriptive statistics, and univariable and multivariable analyses.\n\nThe median age at seizure onset was 9 months. Developmental delay and/or intellectual disability (DD/ID) was observed in 61.3% of the cohort; 38.1% of individuals received an International League Against Epilepsy epilepsy syndrome diagnosis. WGS/WES was performed in 640 (87.3%) and 143 (19.5%) families, respectively, totaling 2029 individuals. A molecular diagnosis was identified in 278 of 733 individuals (37.9%), including 51 of 211 individuals analyzed more than once (24.2% of reanalyzed cases). Independent predictors for receiving a genetic diagnosis included female sex (adjusted odds ratio [aOR] = 1.8, 95% confidence interval [CI] = 1.3-2.4, p < .001), neonatal seizure onset (aOR = 2.5, 95% CI = 1.6-4, p < .001), mortality (aOR = 2.2, 95% CI = 1.3-4.0, p = .0048), and an ID/DD/developmental and epileptic encephalopathy (DEE) diagnosis (aOR = 1.8, 95% CI = 1.2-2.5, p = .0019). The strongest independent predictor of ID/DD/DEE was microcephaly (aOR = 7.8, 95% CI = 2-53, p = .0099). In the solved cohort, gene group did not predict cognitive outcome.\n\nClinical WGS is an effective diagnostic tool in pediatric epilepsy. We identified female sex as a novel prognostic factor for receiving a genetic diagnosis and highlight the value of reanalyzing previously unsolved cases to improve diagnostic yield.", "doi": "10.1111/epi.18403", "pmid": "40183601", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12371643"}], "notes": [], "created": "2025-11-18T20:45:27.809Z", "modified": "2025-11-18T20:45:27.863Z"}, {"entity": "publication", "iuid": "da7a890736f04a11bf851615d6ddf028", "links": {"self": {"href": "https://publications.scilifelab.se/publication/da7a890736f04a11bf851615d6ddf028.json"}, "display": {"href": "https://publications.scilifelab.se/publication/da7a890736f04a11bf851615d6ddf028"}}, "title": "Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study.", "authors": [{"family": "St\u00f6dberg", "given": "Tommy", "initials": "T", "orcid": "0000-0003-1242-5260", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae8c80e14d814232a164040f24fc6acd.json"}}, {"family": "Tomson", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0003-0554-5352", "researcher": {"href": "https://publications.scilifelab.se/researcher/f001d5b4949547e2bb390af5463b50f5.json"}}, {"family": "Barbaro", "given": "Michela", "initials": "M"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Carlsson", "given": "Sofia", "initials": "S"}, {"family": "\u00c5mark", "given": "Per", "initials": "P"}, {"family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "researcher": {"href": "https://publications.scilifelab.se/researcher/15f660ec95994b6a83d540e48c9b7610.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Epilepsia", "issn": "1528-1167", "volume": "61", "issue": "11", "pages": "2486-2499", "issn-l": "0013-9580"}, "abstract": "Population-based data on epilepsy syndromes and etiologies in early onset epilepsy are scarce. The use of next-generation sequencing (NGS) has hitherto not been reported in this context. The aim of this study is to describe children with epilepsy onset before 2 years of age, and to explore to what degree whole exome and whole genome sequencing (WES/WGS) can help reveal a molecular genetic diagnosis.\n\nChildren presenting with a first unprovoked epileptic seizure before age 2 years and registered in the Stockholm Incidence Registry of Epilepsy (SIRE) between September 1, 2001 and December 31, 2006, were retrieved and their medical records up to age 7 years reviewed. Children who met the epilepsy criteria were included in the study cohort. WES/WGS was offered in cases of suspected genetic etiology regardless of whether a structural or metabolic diagnosis had been established.\n\nOne hundred sixteen children were included, of which 88 had seizure onset during the first year of life and 28 during the second, corresponding to incidences of 139 and 42/100 000 person-years, respectively. An epilepsy syndrome could be diagnosed in 54% of cases, corresponding to a birth prevalence of 1/1100. Structural etiology was revealed in 34% of cases, a genetic cause in 20%, and altogether etiology was known in 65% of children. The highest diagnostic yield was seen in magnetic resonance imaging (MRI) with 65% revealing an etiology. WES/WGS was performed in 26/116 cases (22%), with a diagnostic yield of 58%.\n\nEpilepsy syndromes can be diagnosed and etiologies revealed in a majority of early onset cases. NGS can identify a molecular diagnosis in a substantial number of children, and should be included in the work-up, especially in cases of epileptic encephalopathy, cerebral malformation, or metabolic disease without molecular diagnosis. A genetic diagnosis is essential to genetic counselling, prenatal diagnostics, and precision therapy.", "doi": "10.1111/epi.16701", "pmid": "32964447", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7756847"}], "notes": [], "created": "2020-11-22T16:13:01.434Z", "modified": "2021-11-10T12:47:06.774Z"}, {"entity": "publication", "iuid": "23f07fa1366140489ae6b485aefa3f41", "links": {"self": {"href": "https://publications.scilifelab.se/publication/23f07fa1366140489ae6b485aefa3f41.json"}, "display": {"href": "https://publications.scilifelab.se/publication/23f07fa1366140489ae6b485aefa3f41"}}, "title": "Intractable epilepsy of infancy due to homozygous mutation in the EFHC1 gene.", "authors": [{"family": "Berger", "given": "Itai", "initials": "I"}, {"family": "Dor", "given": "Talya", "initials": "T"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Edvardson", "given": "Simon", "initials": "S"}, {"family": "Shaag", "given": "Avraham", "initials": "A"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Elpeleg", "given": "Orly", "initials": "O"}], "type": "case reports", "published": "2012-08-00", "journal": {"volume": "53", "issn": "1528-1167", "issue": "8", "pages": "1436-1440", "title": "Epilepsia", "issn-l": "0013-9580"}, "abstract": "The molecular etiology of primary intractable epilepsy in infancy is largely unknown. We studied a nonconsanguineous Moroccan-Jewish family, where three of their seven children presented with intractable seizures and died at 18-36 months.\n\nHomozygous regions were searched using 250 K DNA single nucleotide polymorphism (SNP) array. The sequence of 50 Mb exome of a single patient was determined using SOLiD 5500XL deep sequencing analyzer.\n\nA single homozygous 11.3 Mb genomic region on chromosome 6 was linked to the disease in this family. This region contained 110 genes encoding a total of 1,000 exons. Whole exome sequencing revealed a single pathogenic homozygous variant within the critical region. The mutation, Phe229Leu in the EFHC1 gene was previously shown, in a carrier state, to be associated with juvenile myoclonic epilepsy.\n\nAlthough heterozygosity for the Phe229Leu mutation is known to be associated with a relatively benign form of epilepsy in adolescence; homozygosity for the same mutation is associated with lethal epilepsy of infancy. Given the considerable carrier rate of this mutation worldwide, the sequence of the EFHC1 gene should be determined in all patients with primary intractable epilepsy in infancy.", "doi": "10.1111/j.1528-1167.2012.03536.x", "pmid": "22690745", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:33.057Z", "modified": "2021-07-07T14:15:07.510Z"}], "created": "2017-05-09T09:12:28.501Z", "modified": "2020-11-27T13:14:04.644Z"}