{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T23:08:51Z","timestamp":1773184131414,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1196637"],"award-info":[{"award-number":["APP1196637"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was undertaken to analyze phenotypic features of a cohort of patients with protracted CLN3 disease to improve recognition of the disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed phenotypic data of 10 patients from six families with protracted CLN3 disease. Haplotype analysis was performed in three reportedly unrelated families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Visual impairment was the initial symptom, with onset at 5\u20139\u2009years, similar to classic CLN3 disease. Mean time from onset of visual impairment to seizures was 12\u2009years (range\u2009=\u20096\u201341\u2009years). Various seizure types were reported, most commonly generalized tonic\u2013clonic seizures; focal seizures were present in four patients. Progressive myoclonus epilepsy was not seen. Interictal electroencephalogram revealed mild background slowing and 2.5\u20133.5\u2010Hz spontaneous generalized spike\u2013wave discharges. Additional interictal focal epileptiform discharges were noted in some patients. Age at death for the three deceased patients was 31, 31, and 52\u2009years. Molecular testing revealed five individuals were homozygous for c.461\u2010280_677\u2009+\u2009382del966, the \"common 1\u2010kb\" <jats:italic>CLN3<\/jats:italic> deletion. The remaining individuals were compound heterozygous for various combinations of recurrent pathogenic <jats:italic>CLN3<\/jats:italic> variants. Haplotype analysis demonstrated evidence of a common founder for the common 1\u2010kb deletion. Dating analysis suggested the deletion arose approximately 1500\u2009years ago and thus did not represent cryptic familial relationship in this Australian cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>We highlight the protracted phenotype of a disease generally associated with death in adolescence, which is a combined focal and generalized epilepsy syndrome with progressive neurological deterioration. The disorder should be suspected in an adolescent or adult patient presenting with generalized or focal seizures preceded by progressive visual loss. The common 1\u2010kb deletion has been typically associated with classic CLN3 disease, and the protracted phenotype has not previously been reported with this genotype. This suggests that modifying genetic factors may be important in determining this somewhat milder phenotype and identification of these factors should be the subject of future research.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17616","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T13:08:35Z","timestamp":1681218515000},"page":"1833-1841","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Recognition and epileptology of protracted <scp>CLN3<\/scp> disease"],"prefix":"10.1111","volume":"64","author":[{"given":"Jillian M.","family":"Cameron","sequence":"first","affiliation":[{"name":"Department of Medicine, Epilepsy Research Centre University of Melbourne, Austin Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Damiano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Epilepsy Research 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