Clinical Phenotype and Omics Study of KCNQ2-related Epilepsy

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.

Study Overview

• Status: Recruiting
• Conditions: KCNQ2-related Epilepsy
• Intervention / Treatment: Other: Electrophysiological detection of KCNQ2 mutation; Other: Multi-modal brain image and EEG; Other: Omics testing

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.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Yi Wang, Dr; Phone Number: 13564766228; Email: yiwang@shmu.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200232
      • Recruiting
      • Children's Hospital of Fudan University
      • Contact: Yi Wang, Dr.; Phone Number: +8613564766228; Email: yiwang@shmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The patients of KCNQ2-related epilepsy who meet the clinical and genetic diagnosis criteria.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BFNS group; (1) Epileptic seizure in neonatal period; (2) Epileptic seizure duration is short, which under spontaneous control in 4~6 months; (3) The patient was in normal state of feeding, physical examination and psychomotor development; (4) There were no signs of hypsarrhythmia or burst suppression in EEG.	Other: Electrophysiological detection of KCNQ2 mutation; Electrophysiological detection of KCNQ2 mutation performed using patch clamp technique in an in vitro cell model. Analyze the association between phenotype and genotype.; Other: Multi-modal brain image and EEG; Multi-modal brain image include brain magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT). The electroencephalogram (EEG) incuding video electroencephalogram (VEEG) and sleep electroencephalogram (SEEG).; Other: Omics testing; Omics testing include proteomics, metabolomics, transcriptomics.
DEE group; (1) Epileptic seizures occur within a week after birth and recur frequently; (2) Epilepsy is refractory; (3) Feeding difficulties, accompanied by moderate to severe mental retardation and psychomotor retardation; (4) The EEG showed hypsarrhythmia or burst suppression.	Other: Electrophysiological detection of KCNQ2 mutation; Electrophysiological detection of KCNQ2 mutation performed using patch clamp technique in an in vitro cell model. Analyze the association between phenotype and genotype.; Other: Multi-modal brain image and EEG; Multi-modal brain image include brain magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT). The electroencephalogram (EEG) incuding video electroencephalogram (VEEG) and sleep electroencephalogram (SEEG).; Other: Omics testing; Omics testing include proteomics, metabolomics, transcriptomics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish the phenotype database and genotype-phenotype association of KCNQ2-related Epilepsy	Analysis of Clinical information of KCNQ2-related Epilepsy such as phenotype, genotype, brain image ,EEG, living quality and comorbidity.	0-18 years old
Study on the brain network of KCNQ2-related epilepsy	Analysis of brain network of KCNQ2-related epilepsy based on multi-modal brain image and EEG	0-18 years old
Study on the omics testing of KCNQ2-related epilepsy	Analysis of prognostic biomarker of KCNQ2-related epilepsy based on proteomics, metabolomics, transcriptomics.	0-18 years old

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Yi Wang, Dr, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): December 15, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Brain network; KCNQ2-related epilepsy; Benign familial neonatal seizures; Developmental and epileptic encephalopathy; Genotype-phenotype association; Omics study
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: 2020-520

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No