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

Seizures Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03934268
• Other study ID #: CHFudanU_NNICU12
• Status: Recruiting
• Start date: January 1, 2017
• Est. completion date: December 2023

Study information

• Verified date: September 2023
• Source: Children's Hospital of Fudan University
• Contact: Wenhao Zhou, Prof.
• Phone: (+86) 021-64931168
• Email: zwhchfu[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Days to 28 Days

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Epilepsy
• Epileptic Encephalopathy
• Epileptic Encephalopathy, Infant-onset
• Epileptic Encephalopathy, Neonatal-onset
• KCNQ2
• Seizure Disorder
• Seizure Newborn
• Seizures
• Seizures, Generalized

Intervention

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

Locations

Country	Name	City	State
China	Children Hospital of Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Fudan University

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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.
Secondary	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.