Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder
Citation Manager Formats
Make Comment
See Comments

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
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.
GLOSSARY
- aa=
- amino acid;
- AED=
- antiepileptic drug;
- CDKL5=
- cyclin-dependent kinase-like-5;
- CI=
- confidence interval;
- IRR=
- incidence rate ratio;
- VNS=
- vagal nerve stimulation
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received March 28, 2016.
- Accepted in final form August 4, 2016.
- © 2016 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Nicole Sur and Dr. Mausaminben Hathidara
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Clinical/Scientific Notes
Persistent antiepileptic effects after vagus nerve stimulation ends?Douglas Labar, Laura Ponticello et al.Neurology, December 22, 2003 -
Articles
MeCP2 mutations in children with and without the phenotype of Rett syndromeK. Hoffbuhr, J. M. Devaney, B. LaFleur et al.Neurology, June 12, 2001 -
Brief Communications
Vagus nerve stimulation for medication-resistant generalized epilepsyDouglas Labar, Jerome Murphy, Evelyn Tecoma et al.Neurology, April 01, 1999 -
Articles
Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutationsF. E. Jansen, O. Braams, K. L. Vincken et al.Neurology, November 21, 2007