KCNQ2 DEE: Lived Experiences and Outcomes¹

Dr. Michele Postashman’s newly published article in Epilepsy & Behavior details a qualitative, lived experience study of individuals and families affected by KCNQ2-DEE. With recruitment help from KCNQ2 Cure Alliance (thank you to those who participated!), they interviewed 53 parents of people with the disorder. Findings show that non-seizure related symptoms like communication difficulties, cognitive delays, and problems with personal care and hygiene are reported as most burdensome. This work aims to inform future clinical trials so that therapeutics can move beyond a sole focus on seizure reduction and address additional quality-of-life symptoms. 

Targeted Gene Panel and Whole Exome Sequencing on DEE Cohort in Turkey²

Using a targeted gene panel, investigators at Kocaeli University in Turkey identified pathogenic or likely pathogenic variants in 29 out of 129 children with symptoms suggestive of DEE. Four had KCNQ2 variants, making it the second most affected gene identified in the panel. These four individuals had heterozygous missense variants in the pore domain (p.T274M, p.A306V) or voltage-sensing domain (p.S195F, p.R207W). All had early onset seizures, and one (with a voltage-sensing domain variant) displayed autism-like features.

Bexicaserin Trial for Developmental Epileptic Encephalopathies (PACIFIC)³

A recent study published in Epilepsia showed that the selective serotonin receptor agonist bexicaserin was well tolerated and effective at reducing motor seizure frequency across a variety of DEE types. While seizure endpoints may be only one of the priorities for the KCNQ2 community, this study’s successful use of a broad category (“DEE Other”) alongside Dravet and Lennox-Gastaut syndromes opens the door for future researchers to use this designation. By showing significant clinical improvement in a diverse pool of people, they provide evidence that aggregating multiple DEEs is a viable approach. Findings like these could lead to increased inclusion of multiple DEEs in future clinical trials.

Some Helpful Definitions

Agonist: A drug that binds to a receptor and activates it

Heterozygous: A person is heterozygous for a gene if one of their copies carries a variant while the other does not

Missense: A type of genetic variant where one piece of the DNA is swapped with another, causing the cell to make a protein that may not work as intended   

Pathogenic: Describes a variant that is known to cause or increase the likelihood of developing a disease

Pore domain: The part of the potassium channel that the KCNQ2 gene encodes that allows potassium ions to travel out of a cell

Targeted Gene Panel: A genetic test that looks at a specific set of genes known to be linked to a certain disease (in this case, DEE)

Voltage-sensing domain: The part of the potassium channel that the KCNQ2 gene encodes that detects changes in the electrical charge across a cell’s membrane to determine whether the channel opens or closes

WORKS CITED 

1. Potashman MH, Rudell K, Abetz-Webb L, Suminski N, Gold A, Doma R, Jarodia K, Buckley C, Ridley M, Lerner J, Mather J, Coric V, Numis AL, Sands TT, Millichap J, Berg AT, L’Italien G. Understanding lived experiences with KCNQ2 developmental and epileptic encephalopathy. Epilepsy Behav. 2025 Nov; 172:110670. doi: 10.1016/j.yebeh.2025.110670. Epub 2025 Sep 4. PMID: 40912075.
2. Sunnetci-Akkoyunlu D, Kara B, Ozer T, Deniz A, Sakarya-Gunes A, Isik EB, Dogruoglu B, Ilkay Z, Yilmaz M, Sahin S, Eren-Keskin S, Cine N, Savli H. Genetic Etiology of Developmental and Epileptic Encephalopathy in a Turkish Cohort: A Single-Center Study with Targeted Gene Panel and Whole Exome Sequencing. Genes (Basel). 2025 Sep 28;16(10):1152. doi: 10.3390/genes16101152. PMID: 41153369; PMCID: PMC12562696.
3. Dlugos DJ, Scheffer IE, French JA, Vossler DG, Orevillo C, Polega S, Kaye R; and the LP352‐201 Study Investigators. Bexicaserin for the treatment of seizures in developmental and epileptic encephalopathies: A phase 1b/2a trial (PACIFIC). Epilepsia. 2025 Oct 24. doi: 10.1111/epi.18689. Epub ahead of print. PMID: 41133912.