KCNQ2-Related Epilepsy: Genotype–Phenotype Relationship with Tailored Antiseizure Medication (ASM)—A Systematic Review

Abstract

Autosomal dominant mutations of KCNQ2 gene cause two epileptic disorders: Benign Familial Infantile Epilepsy (BFIE) and Early Onset Epileptic Encephalopathy (EOEE). Identifying the best reported therapy for these patients is the aim of this systematic Methods: we searched on Pubmed using the search terms “KCNQ2” AND “therapy” and “KCNQ2” AND “treatment”; we found 304 papers, of these, 29 met our criteria. We selected the data of 194 patients. All 29 papers were retrospective studies. Results: 104 patients were classified as EOEE, 90 as BFIE. After starting the treatment, 95% of BFIE became seizure-free while only in 73% of those with EOEE the seizures stopped.. Phenobarbital and sodium channel blockers were the most used treatment in BFIE. Most of the EOEE patients needed polytherapy and in the great majority, their outcome was severely affected (77%). Missense mutations were discovered in 96% of EOEE patients; they were prevalent but with a lower percentage also in BFIE ones (50%), followed by large deletion (16%), truncating (16%), splice donor site (10%) and frameshift (7%). Conclusions: Phenobarbital or Carbamazepine are reported to be the most effectivedrugs for child who have “benign” course, instead polytherapy is often necessary in EOEE patients, even if did not improve their neurological outcome In EOEE patients, mutations were located most frequently in S4 and S6 Helix and this could be an important information for developing new specific drugs.

Distinctive Amplitude-Integrated EEG Ictal Pattern and Targeted Therapy with Carbamazepine in KCNQ2 and KCNQ3 Neonatal Epilepsy: A Case Series

“…Although the underlying causes of the differential developmental trajectories in KCNQ2-related disorders are not fully understood, some genotype-phenotype correlations have emerged, spanning from SLNE with transient seizures in the first month of life to DEE, characterized by neonatalonset seizures with subsequent long-term developmental impairments and later onset disability with and without seizures. 4,[26][27][28] In our case series, we may consider that patients 2, 3, and 5 present a SLNE phenotype, and patients 1 and 4 a DEE phenotype.…”

“…SCB, VPA, and levetiracetam were partially effective without significant differences. 26 In patient 1, CBZ was not trialed but the last ASM to introduce was VPA. In patients 2 and 4, levetiracetam was partially effective.…”

“…In DEE, PB was ineffective as 1 st line ASM. SCB, VPA and levetiracetam were partially effective without significant differences [26]. Patient 1, CBZ was not trialled but the last ASM to introduce was VPA.…”