Relationship Between Polymorphisms of TRPV1 and KCC2 Gene in Children With Febrile Seizures

Institut za Rehabilitaciju Sokobanjska Beograd

Status: Completed

Conditions: Febrile Seizure

Treatments: Genetic: Isolated DNA, Real Time PCR

Study type: Observational

Funder types: Other

Identifiers

NCT04368936

SBCPRN2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 121 patients

Sex: All

Ages: 1 to 14 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

121 participants in 6 patient groups

FS: Febrile Seizures

Description:

Involved patient with diagnosed Febrile Seizures which were hospitalized or recieved ambulatory treatment in University Children´s Hospital in Belgrade. Ages 1-14 years

Treatment:

Genetic: Isolated DNA, Real Time PCR

CN: Control group

Description:

The control group was made of healthy children older than 5 years of age, which have never had any neurological disorders in their anamnesis and who were patients in preschool or school dispensaries in the city of Belgrade

Treatment:

Genetic: Isolated DNA, Real Time PCR

SFS : group of individuals with simple FS

Description:

Simplex febrile seizures (SFS) last shorter than 15 minutes and their type is tonic-clonic. Also, they did not show signs of recidivism during the first 24 hours and were diagnosed at the patients aged from 6th months to 5th year

Treatment:

Genetic: Isolated DNA, Real Time PCR

CFS : group of individuals with complex FS

Description:

Complex febrile seizures (CFS) were diagnosed at those patients that had focal seizure or epileptic status or seizure having the body temperature lower than 38 degree, which occurred outside of the typical age group and finally which repeated in the first 24 hours again

Treatment:

Genetic: Isolated DNA, Real Time PCR

WFS: group of individuals with FS and without epilepsia

Description:

group of children with Febrile Seizure and not developed Epilepsia

Treatment:

Genetic: Isolated DNA, Real Time PCR

EFS: group of individuals with Epilepsia and Febrile Seizures

Description:

Group of children with Febrile Seizures, who have developed Epilepsy

Treatment:

Genetic: Isolated DNA, Real Time PCR