{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T04:20:59Z","timestamp":1780719659943,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100013223","name":"PTC Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013223","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015362","name":"Amicus Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011110","name":"UCB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011110","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016814","name":"Marinus Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016814","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      CDKL5 deficiency disorder (CDD) is a rare X\u2010linked developmental and epileptic encephalopathy caused by loss\u2010of\u2010function variants in the\n                      <jats:italic>CDKL5<\/jats:italic>\n                      gene. Preclinical experiments using enzyme replacement or gene therapies show promise and could be transformative therapies. This precompetitive consortium sought to harmonize nonseizure clinical endpoint selection for efficacy trials. Clinical Assessment of Neurodevelopmental Measures in CDD (CANDID) is an ongoing study evaluating the feasibility and suitability of neurocognitive tests and functioning scales in CDD patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CANDID is a 3\u2010year, longitudinal, noninterventional global study involving children and adults with CDD. On\u2010site and remote visits include clinical, behavioral, developmental, and quality of life assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We enrolled 112 patients (111 included in analyses); mean age\u2009=\u20098.3\u2009years (range &lt;1\u201328); 93% female; 10 participants were \u226518\u2009years old. In the first 28\u2009days, 82% had &gt;16 seizures; six were seizure\u2010free. Median seizure onset was at 1.5\u2009months (range\u2009=\u20090\u201366). Patients used an average of 2.6 antiseizure medications at baseline. The most frequent comorbidities included gastrointestinal hypomotility, muscle tone abnormalities, and sleep disorders. Gross Motor Function Measure\u201088 (GMFM\u201088) scores indicated a floor effect in crawling, standing, and walking across all ages. Vineland\u20103 and Bayley\u20104 scores could be derived in most, with receptive language, interpersonal relationships, and fine and gross motor scores increasing with age. Bruni sleep questionnaire identified sleep initiation, sleep\u2013awake transition, and excessive somnolence as the most disrupted components across all age groups. The mean Quality of Life Inventory\u2013Disability total scores ranged from 53% to 64%, the independence domain being the most impacted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The scales in the CANDID study capture disease\u2010related deficits and phenotype variability in CDD. Floor effects in subdomains aligned with disease severity. The GMFM\u201088 lacks granularity, and its operational limitations make it unsuitable for CDD trials. Baseline analyses demonstrate the feasibility and potential value of most selected scales, supporting their use in optimizing trial design and endpoint selection for future CDD clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70095","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T07:24:24Z","timestamp":1768375464000},"page":"1703-1721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Baseline characteristics and feasibility of clinical outcome measures in\n                    <scp>CDKL5<\/scp>\n                    deficiency disorder: The\n                    <scp>CANDID<\/scp>\n                    observational study"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5994-6487","authenticated-orcid":false,"given":"Xavier","family":"Liogier d'Ardhuy","sequence":"first","affiliation":[{"name":"Loulou Foundation  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"CANDID Partners","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Cimms","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1058-3185","authenticated-orcid":false,"given":"Kristina","family":"Lindsten","sequence":"additional","affiliation":[{"name":"Immedica Pharma  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4838-3796","authenticated-orcid":false,"given":"Marco","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6538-0644","authenticated-orcid":false,"given":"Alison","family":"Skrinar","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4736-0233","authenticated-orcid":false,"given":"Peter","family":"St. Wecker","sequence":"additional","affiliation":[{"name":"UCB Biosciences  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6213-6160","authenticated-orcid":false,"given":"Ana","family":"Mingorance","sequence":"additional","affiliation":[{"name":"Loulou Foundation  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Department of Neurology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.02.015"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000200"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13862"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0418-y"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz195"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.10.037"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-1807"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01520.x"},{"key":"e_1_2_12_10_1","volume-title":"GeneReviews\u00ae","author":"Benke TA","year":"2024"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16285"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00546-6"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37851"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.03.017"},{"key":"e_1_2_12_15_1","unstructured":"GibbonsE SamsL SpecchioN BenkeT CrossJH UtleyK et\u00a0al.Development of a conceptual model for CDKL5 deficiency disorder. Default2019. Available from:https:\/\/aesnet.org\/abstractslisting\/development\u2010of\u2010a\u2010conceptual\u2010model\u2010for\u2010cdkl5\u2010deficiency\u2010disorder"},{"key":"e_1_2_12_16_1","unstructured":"PierceS.stxbp1 and syngap1 related disorders: assessing the feasibility of developmental outcome measures. Default2024. Available from:https:\/\/aesnet.org\/abstractslisting\/stxbp1\u2010and\u2010syngap1\u2010related\u2010disorders\u2010assessing\u2010the\u2010feasibility\u2010of\u2010developmental\u2010outcome\u2010measures"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16750"},{"key":"e_1_2_12_18_1","article-title":"Patient\u2010advocate\u2010led global coalition adapting fit\u2010for\u2010purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials","volume":"5","author":"Hecker J","year":"2024","journal-title":"Ther Adv Rare Dis"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17125"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13600"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2022.104322"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003352"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17886"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2023.107098"},{"key":"e_1_2_12_25_1","unstructured":"Aledo\u2010SerranoA Lewis\u2010SmithD LeonardH BayatA JunaidM HagebeukE et\u00a0al.The natural history of CDKL5 deficiency disorder into adulthood.medRxiv;2025. p. 2025.01.12.24318239. Available from:https:\/\/www.medrxiv.org\/content\/10.1101\/2025.01.12.24318239v1"},{"issue":"3","key":"e_1_2_12_26_1","first-page":"130","article-title":"Caregiver's perception of epilepsy treatment, quality of life and comorbidities in an international cohort of CDKL5 patients","volume":"21","author":"Amin S","year":"2017","journal-title":"Hippokratia"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-022-00921-5"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006729"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14122179"},{"key":"e_1_2_12_30_1","volume-title":"GeneReviews\u00ae","author":"Miceli F","year":"2022"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815599262"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2023.07.007"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70095","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70095","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70095","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:26:21Z","timestamp":1776097581000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/epi.70095"],"URL":"https:\/\/doi.org\/10.1002\/epi.70095","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"assertion":[{"value":"2025-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}