Clinical trial NCT05157737: Clinical Phenotype and Omics Study of KCNQ2-related Epilepsy
Official title: Clinical Phenotype and Omics Study of KCNQ2-related Epilepsy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: KCNQ2-related Epilepsy
Keywords: KCNQ2-related epilepsy
Benign familial neonatal seizures
Developmental and epileptic encephalopathy
Genotype-phenotype association
Brain network
Omics study
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2021-12-15
Enrollment: 200
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The patients of KCNQ2-related epilepsy who meet the clinical and genetic diagnosis criteria.

Brief summary: The aims of study on KCNQ2-related epilepsy: (1) establish phenotype database and sample database of KCNQ2-related epilepsy; (2) to establish genotype-phenotype association of KCNQ2-related epilepsy; (3) to study the brain network of KCNQ2-related epilepsy based on multi-modal brain image and EEG data; (4) to find prognostic biomarkers of KCNQ2-related epilepsy based on omics study.

Detailed description: 1. Participant recruitment: participants are recruited from Chinese KCNQ2-related epilepsy patients group (http://www.kcnq2.cn/). According to the clinical phenotype, the participants will be divided into benign familial neonatal seizures (BFNS) group and Developmental and epileptic encephalopathy (DEE) group.
2. Genotype-phenotype association: electrophysiological detection of KCNQ2 mutation will be performed using patch clamp technique in an in vitro cell model. The association between phenotype (such as epileptic phenotype, developmental assessment and drug response) and genotype will be analyzed.
3. Brain network analysis: participants who provide informed consent will be scaned by brain magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT) and monitored by the electroencephalogram (EEG). The Brain Network of KCNQ2-related epilepsy will be analyzed based on multi-modal brain image and EEG between BFNS and DEE group.
4. Omics Study: after informed consent, blood, urine and feces samples of participants will be taken. The samples were tested for omics study including proteomics, metabolomics, transcriptomics, to analysis the difference of BFNS and DEE group.

Eligibility criteria: Inclusion Criteria:

* KCNQ2 mutation was confirmed by WES, Panel and other gene tests;
* Clinically diagnosed as epilepsy;
* KCNQ2 mutation was identified as pathogenic or possibly pathogenic according to ACMG pathogenicity rating standard;
* Age and gender are not limited;
* No abnormal birth history;
* Informed consent and willingness to follow up

Exclusion Criteria:

* Patients with KCNQ2 mutation without epilepsy;
* Other possible pathogenic gene mutations except KCNQ2;
* Large cross-gene deletions or duplications including KCNQ2;
* Unable to participate in the study follow-up

Primary outcomes:
measure: Establish the phenotype database and genotype-phenotype association of KCNQ2-related Epilepsy
timeFrame: 0-18 years old
measure: Study on the brain network of KCNQ2-related epilepsy
timeFrame: 0-18 years old
measure: Study on the omics testing of KCNQ2-related epilepsy
timeFrame: 0-18 years old
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Yi Wang, Dr
role: PRINCIPAL_INVESTIGATOR
References: