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

NCT03934268 | Unknown DMC

• 1 other identifier: CHFudanU_NNICU12
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Seizures; Seizure Disorder; Seizure Newborn; Seizures, Generalized; Epileptic Encephalopathy; Epileptic Encephalopathy, Neonatal-onset; Epileptic Encephalopathy, Infant-onset; KCNQ2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Recurrence rate of KNCQ2 gene-related convulsion in children under 1 year of age

  From birth to under 1 year of age

• Efficacy of first-line anticonvulsants in children with KCNQ2 gene-related convulsions

  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 infants will be evaluated by bayley Neurodevelopment scale at the age of about two years.

Study Arms (1)

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

Interventions

KCNQ2 GENETIC

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

infants with seizure with KCNQ2 gene mutation.

Eligibility Criteria

• Age: 0 Days - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead

Study Sites (1)

Children Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 30771507 BACKGROUND

• 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.

  PMID: 29426806 BACKGROUND

• 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.

  PMID: 27781560 BACKGROUND

• 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.

  PMID: 26022171 BACKGROUND

• 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.

  PMID: 30242262 RESULT

• 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.

  PMID: 29748663 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

The researchers retained the neonates' or infants' 2ml serum as a biological sample for the Whole Exon Sequencing.

MeSH Terms

Conditions

Seizures; Epilepsy

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Study Officials

• Wenhao Zhou, Prof.

  Children Hospital of Fudan University

  STUDY CHAIR

Central Study Contacts

Wenhao Zhou, Prof.

CONTACT

(+86) 021-64931168; zwhchfu@126.com

Lin Yang, Doctor

CONTACT

(+86)021-64931168; yanglin_fudan@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 1, 2019
• Study Start: January 1, 2017
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)