Genetic Epilepsy With Febrile Seizures(A Family Case Report)

Objective: To analyze the clinical and genetic changes of a family of genetic epilepsy with febrile seizures(GEFS+)in order to expand the phenotype spectrum of GEFS+ and improve the clinicians’ understanding of the disease and summed up the clinical manifestations and genetic progress of minority GEFS+ family.Methods: Pediatric neurology clinic of affiliated hospital of zunyi medical college received a case of Gelao family GEFS+ family in 2015.The clinical data of family were summarized,and then capture epilepsy-related genes using next generation of sequencing in involved members.Results: The phenotype includes:(1)one case of idiopathic children with benign occipital epilepsy : proband,4 years old female,clinical manifestations: she was complex febrile seizures(CFS)before 2 years old months.Two new types of seizures(GTCSs and absence)without fever appeared in 2 years old,phenotype evolved into febrile seizures plus(FS+).New types of focal seizures appeared in 3 years old,and phenotype evolved into PS.The proband had been treated with VPA,LEV and OXC;OXC was ineffective result with seizure duration extended,but VPA and LEV were effective.(2)One case of Dravet syndrome: the proband’s uncle(died in 10 years old,the cause of death is unknown),repeated convulsions after birth,including a variety of seizures with fever-sensitivity,along with mental retardation.(3)One case of FS and Down syndrome:the proband’s brother(7 years old),he had a history of FS,mental development was significantly behind,and special appearance of low nose,eye crack,tongue extension.(4)Four cases of FS: proband’s grandfather,uncle,father,cousin.All affected members were under epilepsy-related genes detection(C.4207C<T).The mutant population mutation rate is very low,does not belong to the polymorphism change.And the expression of SCN1 A heterozygous missense mutation was observed in all affected members except proband’s mother(normal phenotype),which was consistent with phenotype and genotype segregation,mutation leading to coding amino acid changes(p.1596 R <C)located on the S2-S3 loops,and protein function prediction were deleterious.Combined with literature review,GEFS+ has phenotypic and genetic heterogeneity,including FS,FS + and a series of phenotypes;previous GEFS + families with little PS reported.Few GEFS+s areassociated with channel gene mutations such as SCN1 A.SCN1A is the most relevant gene associated with epilepsy,with a wide range of phenotypic spectrum,phenotypic severity is related to mutation location and type.Mutations and pathogenesis of hereditary epilepsy is of great help to achieve individualized treatment and improve prognosis.Conclusion: 1.GEFS+ has phenotypic heterogeneity;PS may be one of GEFS+phenotypic profiling;2.The pathogenesis of GEFS + is related to the mutation of SCN1 A gene.Sodium channelα subunit p.1596 site amino acid changes in patients with sodium channel blockers can aggravate the attack;3.The treatment of poor results,or suspected poor prognosis of patients with reasonable genetic testing and interpretation of the results,help to guide the individual treatment and prognosis assessment;4.The uncertainty of the relationship between GEFS + genotype and phenotype remains to be explored further.