{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T10:03:51Z","timestamp":1777111431320,"version":"3.51.4"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with neurofibromatosis type 1 (NF1) have an increased risk for West syndrome (WS), but the underlying mechanisms linking NF1 and WS are unknown. In contrast to other neurocutaneous syndromes, intracerebral abnormalities explaining the course of infantile spasms (IS) are often absent and the seizure outcome is usually favorable. Several studies have investigated a potential genotype\u2013phenotype correlation between NF1 and seizure susceptibility, but an association was not identified. Therefore, we identified three patients with NF1-related WS (NF1-WS) in a cohort of 51 NF1 patients and performed whole-exome sequencing (WES) to identify genetic modifiers. In two NF1 patients with WS and good seizure outcome, we did not identify variants in epilepsy-related genes. However, in a single patient with NF1-WS and transition to drug-resistant epilepsy, we identified a de novo variant in KCNC2 (c.G499T, p.D167Y) coding for Kv3.2 as a previously undescribed potassium channel to be correlated to epilepsy. Electrophysiological studies of the identified KCNC2 variant demonstrated both a strong loss-of-function effect for the current amplitude and a gain-of-function effect for the channel activation recommending a complex network effect. These results suggest that systematic genetic analysis for potentially secondary genetic etiologies in NF1 patients and severe epilepsy presentations should be done.<\/jats:p>","DOI":"10.1055\/s-0040-1710524","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T22:50:46Z","timestamp":1589237446000},"page":"368-372","source":"Crossref","is-referenced-by-count":21,"title":["Whole-Exome Sequencing in NF1-Related West Syndrome Leads to the Identification of KCNC2 as a Novel Candidate Gene for Epilepsy"],"prefix":"10.1055","volume":"51","author":[{"given":"Niklas","family":"Schwarz","sequence":"first","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Department of Epileptology and Neurology, University of Aachen, Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiltrud","family":"Muhle","sequence":"first","affiliation":[{"name":"Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts University of Kiel, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Rademacher","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts University of Kiel, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Seiffert","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Pendziwiat","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts University of Kiel, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Rohr","sequence":"additional","affiliation":[{"name":"Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Christian-Albrechts University of Kiel, Kiel, Germany"},{"name":"Vancouver General Hospital, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"van Baalen","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts University of Kiel, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingo","family":"Helbig","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts University of Kiel, Kiel, Germany"},{"name":"Children's Hospital of Philadelphia and Perelman School of Medicine University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/jmg.2006.045906","article-title":"Guidelines for the diagnosis and management of individuals with neurofibromatosis 1","volume":"44","author":"R E Ferner","year":"2007","journal-title":"J Med Genet"},{"issue":"05","key":"ref2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/ahg.12026","article-title":"Thirty-nine novel 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