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dc.contributor.authorFehr, S.
dc.contributor.authorWong, K.
dc.contributor.authorChin, R.
dc.contributor.authorWilliams, S.
dc.contributor.authorDe Klerk, N.
dc.contributor.authorForbes, D.
dc.contributor.authorKrishnaraj, R.
dc.contributor.authorChristodoulou, J.
dc.contributor.authorDowns, Jennepher
dc.contributor.authorLeonard, H.
dc.identifier.citationFehr, S. and Wong, K. and Chin, R. and Williams, S. and De Klerk, N. and Forbes, D. and Krishnaraj, R. et al. 2016. Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder. Neurology. 87 (21): pp. 2206-2213.

Objective: To investigate seizure outcomes and their relationships to genotype and functional abilities in individuals with the cyclin-dependent kinase-like-5 (CDKL5) disorder. Methods: Using the International CDKL5 Disorder Database, we identified 172 cases with a pathogenic CDKL5 mutation. We categorized individual mutations into 4 groups based on predicted structural and functional consequences. Negative binomial regression was used to model the linear association between current seizure rate and mutation group, current level of assistance required to walk 10 steps, and the highest level of expressive communication used to convey refusal or request. Results: All but 3 (169/172) patients had a history of epilepsy. The median age at seizure onset was 6 weeks (range 1 week-1.5 years) and the median seizure rate at ascertainment was 2 per day (range 0-20 per day). After adjusting for walking ability and confounders including use or otherwise of polytherapy, seizure rate was lower in those with truncating mutations between aa172 and aa781 compared to those with no functional protein (incidence rate ratio [IRR] 0.57; 95% confidence interval [CI] 0.35-0.93). Ability to walk and use of spoken language were associated with lower rates of current seizures when compared to those with the least ability after adjusting for genotype (walking: IRR 0.62; 95% CI 0.39-0.99, communication: IRR 0.48; 95% CI 0.23-1.02). At a median age at questionnaire completion of 5 years, those previously treated with corticosteroids had more frequent seizures than those who have never been treated, whether or not there was a history of infantile spasms. Conclusions: Epilepsy is pervasive but not mandatory for the CDKL5 disorder. Genotype and functional abilities were related to seizure frequency, which appears refractory to antiepileptic drugs.

dc.publisherLippincott Williams & Wilkins
dc.titleSeizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder
dc.typeJournal Article
curtin.departmentSchool of Physiotherapy and Exercise Science
curtin.accessStatusFulltext not available

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