Clinical trial NCT03934268: A Cohort Study on the Prognosis of Neonatal KCNQ2 Gene-associated Epileptic Encephalopathy
Official title: A Cohort Study on the Prognosis of Neonatal KCNQ2 Gene-associated Epileptic Encephalopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Seizures
Seizure Disorder
Seizure Newborn
Seizures, Generalized
Epileptic Encephalopathy
Epileptic Encephalopathy, Neonatal-onset
Epileptic Encephalopathy, Infant-onset
KCNQ2
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2019-05-01
Enrollment: 100
Sex: ALL
Minimum age (years): 0
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of seizure in children with KCNQ2 within 28 days of age
timeFrame: From birth to under 28 days of age
Secondary outcomes:
measure: Recurrence rate of KNCQ2 gene-related convulsion in children under 1 year of age
timeFrame: From birth to under 1 year of age
measure: Efficacy of first-line anticonvulsants in children with KCNQ2 gene-related convulsions
timeFrame: From the beginning of drug intervention to 72 hours after taking the drug.
measure: Proportion of infants classified as having "developmental delay" (MDI <70 on BSID-III or either Language or Cognitive Score <70 on the Bayley-III)
timeFrame: The infants will be evaluated by bayley Neurodevelopment scale at the age of about two years.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children Hospital of Fudan University
name: Wenhao Zhou, Prof.
role: STUDY_CHAIR
References:
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.
citation: 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.
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.
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.
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.
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.