Please use this identifier to cite or link to this item:
Title: Recognition and Epileptology of Protracted CLN3 Disease.
Austin Authors: Cameron, Jillian M ;Damiano, John A;Grinton, Bronwyn;Carney, Patrick W ;McKelvie, Penny;Silbert, Peter;Lawn, Nicholas;Scheffer, Ingrid E ;Oliver, Karen L;Hildebrand, Michael S ;Berkovic, Samuel F 
Affiliation: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia.;Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.
Department of Pathology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, University of Western Australia, Australia.
Royal Perth Hospital, Perth, Western Australia, Australia.
The Florey Institute of Neuroscience and Mental Health
Issue Date: 11-Apr-2023 2023
Publication information: Epilepsia 2023
Abstract: To analyse phenotypic features of a cohort of patients with protracted CLN3 disease to improve recognition of the disorder. We analysed phenotypic data of ten patients from six families with protracted CLN3 disease. Haplotype analysis was performed in three reportedly unrelated families. Visual impairment was the initial symptom with onset at 5-9 years, similar to classic CLN3 disease. Mean time from onset of visual impairment to seizures was 12 years (range 6-41 years). Various seizure types were reported, most commonly generalized tonic-clonic seizures (GTCS); focal seizures were present in four patients. Progressive myoclonus epilepsy was not seen. Inter-ictal EEG revealed mild background slowing and 2.5-3.5Hz spontaneous generalized spike-wave discharges. Additional inter-ictal focal epileptiform discharges were noted in some patients. Age at death for the three deceased patients was 31, 31 and 52 years. Molecular testing revealed five individuals were homozygous for c.461-280_677+382del966, the 'common 1 kilobase pair' CLN3 deletion. The remaining individuals were compound heterozygous for various combinations of recurrent pathogenic CLN3 variants. Haplotype analysis demonstrated evidence of a common founder for the common 1 kb deletion. Dating analysis suggested the deletion arose approximately 1,500 years ago. and thus did not represent cryptic familial relationship in this Australian cohort. 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 1kB 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.
DOI: 10.1111/epi.17616
ORCID: 0000-0003-4880-2486
Journal: Epilepsia
PubMed URL: 37039534
ISSN: 1528-1167
Type: Journal Article
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Jun 2, 2023

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.