A Cohort Study on the Prognosis of Neonatal KCNQ2 Gene-associated Epileptic Encephalopathy

The researchers hope to explore the etiological distribution and influencing factors of KCNQ2-related neonatal convulsions or refractory epileptic encephalopathy, and to improve the level of assessment, identification, intervention and shunt of KCNQ2-related convulsions. To formulate countermeasures and measures for prevention, management and health education.

Study Overview

• Status: Recruiting
• Conditions: Seizures; Seizure Disorder; Epileptic Encephalopathy; Seizures, Generalized; Seizure Newborn; Epileptic Encephalopathy, Neonatal-onset; Epileptic Encephalopathy, Infant-onset; KCNQ2
• Intervention / Treatment: Genetic: KCNQ2

Detailed Description

Convulsion is the most common clinical manifestation of neonatal central nervous system dysfunction. the incidence of convulsion is very high in neonatal period, especially in the first week after birth. the incidence of convulsion decreases gradually with the increase of age. The incidence of convulsion reported by Bassan et al was 1.5 ‰ ~ 3.5 ‰ in term infants and 10% ≤ 130% in premature infants. Most of the neonatal convulsions suggest that there are serious primary diseases in the body. in addition to hypoxic-ischemic encephalopathy, intracranial hemorrhage and infection, a large number of studies have proved that genetic factors play a key role in the occurrence of neonatal convulsions and epileptic encephalopathy in infants. Nearly 20% to 50% of neonatal convulsions are idiopathic convulsions. it has been thought that KCNQ2 gene, a potassium channel subunit located in 20q11.3, and KCNQ3 gene, another potassium channel subunit located in 8q24, are mutated. Is the molecular basis for some benign familial neonatal convulsions, Usually the prognosis is good, but with the expansion of the study sample, investigators found that KCNQ2 may be associated with refractory epileptic encephalopathy, and there are few international reports in this regard. The study of KCNQ2 gene has led to a new understanding of the etiology of neonatal convulsion. The researchers hope to explore the etiological distribution and influencing factors of KCNQ2-related neonatal convulsions or refractory epileptic encephalopathy, and to improve the level of assessment, identification, intervention and shunt of KCNQ2-related convulsions. To formulate countermeasures and measures for prevention, management and health education.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Wenhao Zhou, Prof.; Phone Number: (+86) 021-64931168; Email: zwhchfu@126.com
• Study Contact Backup: Name: Lin Yang, Doctor; Phone Number: (+86)021-64931168; Email: yanglin_fudan@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Recruiting
      • Children Hospital of Fudan University
      • Contact: Wenhao Zhou, Doctor; Phone Number: (+86)021-64931003; Email: zwhchfu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 3 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The subjects came from sub-central hospitals and the newborns were hospitalized in the neonatal department for primary seizure.

Description

Inclusion Criteria:

• Primary or initial convulsion
• Postnatal age <28 days.
• Seizure in the neonatal period
• Informed consent of parents

Exclusion Criteria:

• Seizure caused by congenital cerebral hypoplasia or multiple structural malformations.
• Seizure caused by other system-related syndromes.
• Seizure caused by perinatal or postpartum factors such as HIE, infection, intracranial hemorrhage, etc.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

infants with seizure with KCNQ2 gene mutation.; Infants who met the inclusion criteria were enrolled in this study. The infants will get their own DNA sequencing results by WES technology. The researchers found that some of them carried mutations in the KCNQ2 gene. so they wanted to compare whether there were differences with or without KCNQ2 gene mutations in the efficacy of anticonvulsants or long-term neurodevelopment in different exposure groups.

Genetic: KCNQ2; The researchers extracted DNA from the baby's serum and sent it to WES to get the baby's total exon sequence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of seizure in children with KCNQ2 within 28 days of age	The investigators used WES to screen for neonatal onset seizure and calculated the incidence of KCNQ2 gene mutations in these neonates.	From birth to under 28 days of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate of KNCQ2 gene-related convulsion in children under 1 year of age	Some neonates with seizure associated with KCNQ2 gene mutation will develop epileptic encephalopathy or syndrome at a later stage. The researchers calculated the probability of recurrent seizures or progression in neonates with seizure associated with KCNQ2 gene mutations within the age of one year.	From birth to under 1 year of age
Efficacy of first-line anticonvulsants in children with KCNQ2 gene-related convulsions	Some non-benign KCNQ2 gene-related convulsions require anticonvulsant intervention, and investigators hope to observe and obtain the effective rate of first-line anticonvulsant intervention. To determine whether the convulsion stopped or the frequency of convulsion decreased within 72 hours after taking the drug. If convulsions stop or the frequency of seizures decreases, drug intervention is considered effective.	From the beginning of drug intervention to 72 hours after taking the drug.
Proportion of infants classified as having "developmental delay" (MDI <70 on BSID-III or either Language or Cognitive Score <70 on the Bayley-III)	The investigators plan to use the bayley Neurodevelopmental scale to assess the neurodevelopmental status of infants with KCNQ2 gene-associated epileptic encephalopathy within 2 years of age.	The infants will be evaluated by bayley Neurodevelopment scale at the age of about two years.

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Study Chair: Wenhao Zhou, Prof., Children Hospital of Fudan University

Publications and helpful links

General Publications

• Kuersten M, Tacke M, Gerstl L, Hoelz H, Stulpnagel CV, Borggraefe I. Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review. Eur J Med Genet. 2020 Jan;63(1):103628. doi: 10.1016/j.ejmg.2019.02.001. Epub 2019 Feb 14.
• Cornet MC, Sands TT, Cilio MR. Neonatal epilepsies: Clinical management. Semin Fetal Neonatal Med. 2018 Jun;23(3):204-212. doi: 10.1016/j.siny.2018.01.004. Epub 2018 Jan 31.
• Reif PS, Tsai MH, Helbig I, Rosenow F, Klein KM. Precision medicine in genetic epilepsies: break of dawn? Expert Rev Neurother. 2017 Apr;17(4):381-392. doi: 10.1080/14737175.2017.1253476. Epub 2016 Nov 10.
• Hani AJ, Mikati HM, Mikati MA. Genetics of pediatric epilepsy. Pediatr Clin North Am. 2015 Jun;62(3):703-22. doi: 10.1016/j.pcl.2015.03.013.
• Manville RW, Abbott GW. Ancient and modern anticonvulsants act synergistically in a KCNQ potassium channel binding pocket. Nat Commun. 2018 Sep 21;9(1):3845. doi: 10.1038/s41467-018-06339-2.
• Manville RW, Papanikolaou M, Abbott GW. Direct neurotransmitter activation of voltage-gated potassium channels. Nat Commun. 2018 May 10;9(1):1847. doi: 10.1038/s41467-018-04266-w.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Brain Diseases
• Other Study ID Numbers: CHFudanU_NNICU12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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