{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:57:44Z","timestamp":1789070264582,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Legius syndrome is a rare genetic disorder, caused by heterozygous <jats:italic>SPRED1<\/jats:italic> pathogenic variants, which shares phenotypic features with neurofibromatosis type 1 (NF1). Both conditions typically involve caf\u00e9\u2010au\u2010lait macules, axillary freckling, and macrocephaly; however, patients with NF1 are also at risk for tumors, such as optic nerve gliomas and neurofibromas. Seizure risk is known to be elevated in NF1, but there has been little study of this aspect of Legius syndrome. The reported epilepsy incidence is 3.3%\u20135%, well above the general population incidence of ~0.5%\u20131%, but the few reports in the literature have very little data regarding epilepsy phenotype. We identified two unrelated individuals, both with Legius syndrome and epilepsy, and performed thorough phenotyping. One individual's mother also had Legius syndrome and now\u2010resolved childhood epilepsy, as well as reports of more distant relatives who also had multiple caf\u00e9\u2010au\u2010lait macules and seizures. Both probands had experienced childhood\u2010onset focal seizures, with normal brain MRI. In one patient, EEG later showed apparently generalized epileptiform abnormalities. Based on the data from this small case series and literature review, seizure risk is increased in people with Legius syndrome, but the epilepsy prognosis appears to be generally good, with patients having either self\u2010limited or pharmacoresponsive courses.<\/jats:p>","DOI":"10.1002\/ajmg.a.63547","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T04:39:06Z","timestamp":1706157546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epilepsy in Legius syndrome: Coincidence or causation?"],"prefix":"10.1002","volume":"194","author":[{"given":"Adalbeis","family":"Medina Lemus","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Pediatrics, Montreal Children's Hospital McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Boelman","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7831-4593","authenticated-orcid":false,"given":"Kenneth A.","family":"Myers","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics, Montreal Children's Hospital McGill University Health Centre  Montreal Quebec Canada"},{"name":"Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Department of Neurology and Neurosurgery, Montreal Children's Hospital McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17323"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2113"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21404"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01532-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1990.tb03600.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.0473"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01618.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01170-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac376"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1663"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61921"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2017.05.011"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01579.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153523"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1669"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.67.2.178"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/35088082"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0277-4"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63547","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T19:01:26Z","timestamp":1714503686000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63547"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,24]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/ajmg.a.63547"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63547","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,24]]},"assertion":[{"value":"2023-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63547"}}