| ObjectiveFebrile seizures(FS)are the most common seizure disorder in infants and young children.FS are associated with a higher risk of epilepsy,especially for certain types of epilepsy and epileptic syndromes that begin with FS and exhibit a "fever-sensitive" characteristic,making it difficult to distinguish from FS in the early stages.This study aims to investigate the correlation between clinical phenotype and genetic phenotype in FS/FS+ patients who have a high risk of recurrence and undergo thermal sensitivity gene screening and follow-up to assess their prognosis.This will provide a theoretical basis for the prognosis evaluation of FS/FS+,early identification of feversensitive epilepsy,accurate treatment,and even family genetic counseling.MethodsA total of 109 cases of children under the age of 1 who presented with frequent febrile seizures or febrile seizures plus and were treated in the neurology department of Shanxi Children’s Hospital from February 2019 to March 2022 were selected.Clinical data including gender,age,seizure type,seizure duration,seizure frequency,family history,developmental history,perinatal history,head MRI,EEG,blood and urine metabolic screening,medication history,and other clinical information were collected.Children who met the inclusion criteria were screened,and informed consent was obtained from the children and their guardians who agreed to participate in the study and signed an informed consent form.Two milliliters of blood samples were collected from the children and their parents and sent to Majikno Laboratory for high-throughput technology sequencing of 189 febrile seizure-related genes,including SCN1 A,PRRT2,KCNQ2,TSC2,GFAP,ATP1A2,FKTN,MAGI2,and others.Subsequently,family analysis experiments and first-generation verification were performed.Based on the results of the genetic testing,clinical phenotype,clinical data,physical examination,and auxiliary examination results,the clinical diagnosis was determined by clinical physicians,and a reasonable treatment,follow-up,and evaluation plan was developed.ResultsThere were 109 patients in the study,including 67 males and 42 females.Fourteen patients were aged ≤1 year,77 patients were aged between 1 and 6 years,and 18 patients were aged ≥6 years.The duration of seizures was <15 minutes for 81 patients,15-30 minutes for 23 patients,and >30 minutes for 5 patients.The number of seizures was 5-10 for 81 patients,10-20 for 20 patients,and >20 for 8 patients.There were 61 patients with a family history of seizures and 48 patients without.Of the 86 patients with febrile seizures,50 had simple febrile seizures,36 had complex febrile seizures,and 23 had febrile seizures plus.At the time of enrollment,all patients had normal intellectual and motor development,with normal head MRI results for 101 patients and non-specific abnormalities such as widened extracranial spaces for 8patients.Ninety-nine patients had normal EEG results,while 10 patients had non-specific abnormalities such as scattered slow waves.Ninety-eight patients had normal perinatal histories,while 11 had mild complications such as nuchal cord and premature rupture of membranes.All patients had normal growth and development histories and blood and urine metabolic screening results.After screening 109 patients,20 were found to have mutations in10 pathogenic genes.These gene mutations include SCN1 A,PCDH19,GABRB3,GABRG2,ASAH1,ADRB1,CDKL5,GLB1,ST3GAL5,and MEF2 C.There were 8 cases of SCN1 A gene mutations,3 cases of PCDH19 gene mutations,2 cases of GABRB3 gene mutations,and 1case each of GABRG2,ASAH1,ADRB1,CDKL5,GLB1,ST3GAL5,and MEF2 C gene mutations.During a 1-3 year follow-up of the 109 patients,10 cases developed epilepsy,including patients 1,2,4,7,8,9,10,11,13,and 14.Among the 5 cases of SCN1 A mutations,3 had Dravet syndrome(DS),and 2 had FS+ accompanied by seizures and FS+ accompanied by myoclonus.All 3 cases of PCDH19 mutations were PCDH19-related epilepsy.One case of GABRB3 mutation developed into DS,and one case of GABRG2 mutation developed into benign childhood epilepsy with centrotemporal spikes.ConclusionThe etiology and pathogenesis of febrile seizures(FS)are complex,and genetic factors may play a key role in the onset of the disease.This study screened for thermosensitive genes in 109 children who had their first FS before the age of one and frequently experienced FS/FS+.It was found that FS/FS+ was associated with mutations in multiple genes,with SCN1 A being the main hotspot gene,followed by PCDH19 and GABRB3 genes.Early thermosensitive epilepsy is difficult to distinguish from FS,but screening for hotspot genes in FS/FS+ can identify thermosensitive epilepsy early and take appropriate treatment to avoid serious complications.Genetic counseling can also be provided to high-risk families and help assess the risk of recurrence in other family members,which is of great significance for improving the overall prognosis of FS families. |
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