Exploring the Susceptibility to Tardive Dyskinesia in Patients with a kcnq2-related Disorder
Abstract number :
3.369
Submission category :
12. Genetics / 12A. Human Studies
Year :
2022
Submission ID :
2203912
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:22 AM
Authors :
Brandon Oby, BS – Boston Children's Hospital; Devon Knight, BS – Neurology – Boston Children's Hospital; Sonal Mahida, MGC, CGC – Neurology – Boston Children's Hospital; Heather Olson, MD, MS – Neurology – Boston Children's Hospital; Christelle Moufawad El Achkar, MD – Neurology – Boston Children's Hospital; Annapurna Poduri, MD, MPH – Neurology – Boston Children's Hospital
This abstract has been invited to present during the Broadening Representation Inclusion and Diversity by Growing Equity (BRIDGE) poster session
Rationale: Pathogenic variants in the KCNQ2 gene are associated with a variety of epilepsy and neurodevelopmental disorders with some children presenting with movement disorders. Tardive dyskinesia (TD) is a medication-induced hyperkinetic movement disorder associated with the use of medications for neuropsychiatric conditions, which are often dopamine receptor-blocking agents. Patients with a KCNQ2-related disorder may be prescribed antipsychotic medications for concurrent neurodevelopmental disorders. Here we report a cohort of 44 patients with pathogenic variants in KCNQ2 and highlight individuals who had an onset of TD symptoms after the initiation of an antipsychotic medication.
Methods: Pediatric patients with previously identified variants in KCNQ2 were enrolled in a Boston Children’s Hospital IRB-approved Natural History Study. Recruitment of participants was facilitated by the KCNQ2 Cure Alliance Foundation, self-referral, and physician referral. We collected medical, genetic, and family history information by review of medical records and parent completion of a detailed questionnaire. From the Natural History Study, we focused specifically on patients who developed TD symptoms after the initiation of medications for neuropsychiatric conditions.
Results: We report phenotype and genotype data for 44 individuals enrolled in a natural history study, the largest KCNQ2 cohort to date. We identified 3 patients from the KCNQ2 Natural History Study, each of which had a known pathogenic variant in the KCNQ2 gene. Each participant was prescribed an antipsychotic medication during their treatment for varying reasons. Following initiation of these medications, each participant reported symptoms indicative of a movement disorder and after termination of the medication, had partial improvement.
Conclusions: We suspect that individuals with pathogenic variants in KCNQ2 may be more susceptible to negative side effects associated with antipsychotic medications. As KCNQ2 is expressed in the basal ganglia as well as the cerebral cortex, it is possible that individuals with KCNQ2 variants may have increased susceptibility to side effects associated anti-psychotic medications, including TD. Our observations in the patients described here suggest the need for more detailed analysis of the effects of antipsychotic medication on patients with KCNQ2-related disorders.
Funding: KCNQ2 Alliance and BCH Translational Research Program
Genetics