Clinical Phenotype and Omics Study of KCNQ2-related Epilepsy

Recruiting

• Conditions: KCNQ2-related Epilepsy
• Interventions: Other: Electrophysiological detection of KCNQ2 mutation; Other: Multi-modal brain image and EEG; Other: Omics testing

• Registration Number: NCT05157737
• Lead Sponsor: Fudan University

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.

Study Timeline

• Study Start: 2021-01-01
• Status Verified: 2021-12
• Study First Submitted: 2021-12-01
• Study First Submitted QC: 2021-12-01
• Last Update Submitted: 2021-12-01
• Study First Posted: 2021-12-15
• Last Update Posted: 2021-12-15
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
DEE group	Multi-modal brain image and EEG	(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.
BFNS group	Omics testing	(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.
DEE group	Omics testing	(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.
BFNS group	Electrophysiological detection of KCNQ2 mutation	(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.
BFNS group	Multi-modal brain image and EEG	(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.
DEE group	Electrophysiological detection of KCNQ2 mutation	(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.

Primary Outcome Measures

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

Trial Locations

Locations (1)

Children's Hospital of Fudan University; 🇨🇳 Shanghai, Shanghai, China