Clinical trial NCT04368936: Relationship Between Polymorphisms of TRPV1 and KCC2 Gene in Children With Febrile Seizures
Official title: Relationship Between Polymorphisms of TRPV1 and KCC2 Gene in Children With Febrile Seizures
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Febrile Seizure
Keywords: gene polymorphisms
febrile seizure
KCC2 gene
TRPV1 gene
Lead sponsor: Institut za Rehabilitaciju Sokobanjska Beograd
Sponsor class: OTHER
First posted: 2020-04-30
Enrollment: 121
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: The Febrile Seizure affected children as well as the individuals from the control group were members of the same population (Serbian).

Brief summary: Febrile seizures (FS) are the most common neurological disorder in chilhood. The etiology of FN is still the subject of numerous studies and it is known that it can depend on genetic predisposition.

Detailed description: Febrile seizures (FS) are the most common neurological disorder in chilhood. It is precisely because of the high incidence of the disease, the age that includes the tendency of repetition, represent a particular challenge in pediatric practice.

FS, as defined by the American Academy of Pediatrics (AAP), are " seizure occurring in febrile children between the ages of 6 and 60 months who do not have an intracranial infection, metabolic disturbance, or history of afebrile seizures ".

Simple febrile seizure is defined as a short (\<15 min) generalized seizure, not repeat within 24 h, that occurs during a febrile illness not resulting from an acute disease of the nervous system in a child aged between 6 months and 5 years, with no neurologic deficits and no previous afebrile seizures. Complex febrile seizures are a focal, or generalized and prolonged seizure, of a duration of greater than 15 min, recurring more than once in 24 h, and/or associated with postictal neurologic abnormalities, more frequently a postictal palsy (Todd's palsy), or with previous neurologic deficits.

The etiology of FN is still the subject of numerous studies and it is known that it can depend on genetic predisposition.

Animal studies have shown that mice without the KCC2 gene have frequent generalized seizures, while those with heterozygous deletion of the KCC2 gene have a reduced threshold for seizure onset. In the human population, mutations of this gene have been reported in children with FN as well as in children with epilepsy. There is no examined an association between polymorphism rs2297201 KCC2 gene and FS.

Studies have shown an association between TRPV1 genes and the appearance of FS in experimental models, however, similar studies in the human population have not been done so far. Studies Moria et al. 2012 showed that polymorphism rs222797 TRPV1 gene involve the regulation of human cortical excitability, glutamate transmission and increased neuronal excitability. The C allele this polymorphism is associated with a greater maximal response to the caspaicin and anadamine agonists. All of this indicate that changes TRPV1 gene that lead to increased channel function may suggest a predisposition for FS.

Since FS are genetically controlled, we want to determine the association of TRPV1 and KCC2 gene polymorphisms with the occurrence of FN.

Eligibility criteria: Inclusion Criteria:

* Our research involve patient with diagnosed Febrile Seizure which were hospitalized or recieved ambulatory treatment in University Children´s Hospital in Belgrade
* For each patient, a diagnosis of FS was made based on the ILAE definition (International Leage
* The main criterion for inclusion in the study was enhanced FS without prior occurrence of afebrile seizure.

Exclusion Criteria:

* Patients with evidence of intracranial infections and metabolic disbalance
* Patients with incomplited medical documentation

Primary outcomes:
measure: Detection of the polymorphism in the TRPV1 gene polymorphisms
timeFrame: 2 weeks
measure: Detection of the polymorphism in the KCC2 gene polymorphisms
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Specila hospital for cerebral palsy and developmental neurology
name: Sanja Dimitrijevic, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Huang WX, Yu F, Sanchez RM, Liu YQ, Min JW, Hu JJ, Bsoul NB, Han S, Yin J, Liu WH, He XH, Peng BW. TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain. Brain Behav Immun. 2015 Aug;48:68-77. doi: 10.1016/j.bbi.2015.01.017. Epub 2015 Mar 20.
citation: Xu H, Tian W, Fu Y, Oyama TT, Anderson S, Cohen DM. Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene. Am J Physiol Renal Physiol. 2007 Dec;293(6):F1865-76. doi: 10.1152/ajprenal.00347.2007. Epub 2007 Oct 3.