Kcnq2 encodes the Kv7.2 channel subunit. The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential [2]. Kcnq2-related channels have emerged as a target for novel antiepileptic drugs as their activation could reduce epileptic activity [4]. Mouse models have been developed to study Kcnq2-related pathological mechanisms [1].

Variants in Kcnq2 cause epileptic disorders, ranging from benign forms with self-limited seizures and normal development to severe forms with intractable seizures and encephalopathy [1]. The severe form remains intractable in patients. In Kcnq2-related epilepsy, missense mutations are common in developmental epileptic encephalopathy (DEE) patients. Phenobarbital or carbamazepine may be effective for “benign” variants, while DEE patients often need polytherapy with limited improvement in neurological outcomes [5]. Some patients with Kcnq2 epileptic encephalopathy may respond to pyridoxine treatment [3,6].

In conclusion, Kcnq2 is crucial for stabilizing the neuronal membrane potential through the M-current. Mouse models have been invaluable in understanding the pathological mechanisms of Kcnq2-related epileptic disorders, which can present with a wide range of phenotypes. The study of Kcnq2 provides insights into potential therapeutic strategies for these epilepsy-related diseases.

References:

1. Brun, Lucile, Viemari, Jean-Charles, Villard, Laurent. 2022. Mouse models of Kcnq2 dysfunction. In Epilepsia, 63, 2813-2826. doi:10.1111/epi.17405. https://pubmed.ncbi.nlm.nih.gov/36047730/

2. Ma, Demin, Zheng, Yueming, Li, Xiaoxiao, Gao, Zhaobing, Guo, Jiangtao. 2023. Ligand activation mechanisms of human KCNQ2 channel. In Nature communications, 14, 6632. doi:10.1038/s41467-023-42416-x. https://pubmed.ncbi.nlm.nih.gov/37857637/

3. Chen, Jun, Tao, Qiuji, Fan, Lijuan, Liang, Mengmeng, Gan, Jing. 2022. Pyridoxine-responsive KCNQ2 epileptic encephalopathy: Additional cases and literature review. In Molecular genetics & genomic medicine, 10, e2024. doi:10.1002/mgg3.2024. https://pubmed.ncbi.nlm.nih.gov/35906921/

4. Springer, Kristen, Varghese, Nissi, Tzingounis, Anastasios V. 2021. Flexible Stoichiometry: Implications for KCNQ2- and KCNQ3-Associated Neurodevelopmental Disorders. In Developmental neuroscience, 43, 191-200. doi:10.1159/000515495. https://pubmed.ncbi.nlm.nih.gov/33794528/

5. Falsaperla, Raffaele, Criscione, Roberta, Cimino, Carla, Pisani, Francesco, Ruggieri, Martino. 2023. KCNQ2-Related Epilepsy: Genotype-Phenotype Relationship with Tailored Antiseizure Medication (ASM)-A Systematic Review. In Neuropediatrics, 54, 297-307. doi:10.1055/a-2060-4576. https://pubmed.ncbi.nlm.nih.gov/36948217/

6. Chow, Chit Kwong, Luk, Ho Ming, Wong, Suet Na. 2020. KCNQ2 Encephalopathy and Responsiveness to Pyridoxal-5'-Phosphate. In Journal of pediatric genetics, 12, 90-94. doi:10.1055/s-0040-1721384. https://pubmed.ncbi.nlm.nih.gov/36684546/