Prognosis Studies And Verification Studies Of The Genome-wide Copy Number Variations With Landau-Kleffner Syndrome

PART1Clinical features of40patients with Landau-Kleffner syndrome and prognosis with Landau-Kleffner syndromeObjective:?To retrospectively analysize the clinical features of LKS and do prospective study about prognosis of steroid therapy;?To discuss the clinical features of refractory LKS and do the curative effect analysis of ketogenic diet for refractory LKS.Methods:Forty patients with LKS were enrolled in the Children's Hospital of Fudan University from July2005to February2013.?Retrospectively analysis the clinical features including aphasia, epilepsy, cognition and EEG;?Course and dosage of steroid therapy:Methylprednisolone was given via intravenous infusion at5-20mg/kg daily for3consecutive days, and repeated three times with a4-day interval between treatments. After that prednisolone was given orally (2mg/kg daily for1month, then gradually wean off);?Set up assessment scale for prognosis by ourselves, use the same scale to evaluate a. The prognosis of aphasia(record the onset time, effect initiating time, full-recovery time or no longer improve time provided by parents); b. Comprehensive prognosis of LKS. Grade depends on the prognosis of aphasia, epilepsy and mentality at different course of treatment, and range from grade I (totally recovered) to grade IV (ineffectiveness);?Analysize the clinical features of refractory LKS, treat them with ketogenic diet (classic Johns Hopkins therapy) and observe the curative effect.Results:1. General data:Forty patients were enrolled including20male and20female.Their age ranged from29to192months (median age62months). The onset age of aphasia was from15to168month (median age50months). The course from onset to diagnosis was from10days to7years (median age6months);2. Clinical features:?aphasia:All40patients had auditory agnosia and expressive problem.8patients (20.0%) had expressive aphasia as their main problem and the other32patients (80.0%) had auditory agnosia as their main problem;21patients (52.5%) had completeness aphasia and19patients (47.5%) had partial aphasia.?Epilepsy:27patients (67.5%) had epileptic seizure,18of them (66.7%) had epilepsy before aphasia and9of them (33.3%) had epilepsy after that; Single seizure accounted for16patients (59.3%) and multiple seizure accounted for11patients (40.7%).?Cognitive assessment:37patients were proved to have abnormal mental index by developmental screen test and the left3patients were at normal range by intelligence test.?EEG:28patients (70.0%) had normal background activity and the other12patient (30.0%) had mild slow background activity;32patients (80.0%) had epileptiform discharges, and8patients (20.0%) had normal EEG;10patients had electrical status epilepticus during sleep (ESES)(25.0%).3.Prognosis:?There were31patients taking steroid as their first treatment for LKS, aphasia:median of onset time(Tl) was3weeks in30cases, median of effect initiating time(T2) was3months in23cases, median of full-recovery time(T3) was9months in18cases and median of no longer improve time(T4) was10months in8cases; Comprehensive prognosis:?Overall, steroid therapy was effective in most patients, with the follow-up time extending, the patients with grade I increased and the patients with grade IV became0; the percentage of grade I was nearly50%;18months could be referential time for prognosis;?6refractory LKS (refractory epilepsy, steroid resistance for aphasia and mental retardation) were treated with ketogenic diet,3cases quit at the startup phase, and the other3cases completed the treatment and were followed up to, one had grade II (the course of ketogenic diet was15months), the other two were both grade IV (the course of ketogenic diet was from6?7months).Conclusion:?The clinical features of LKS were complex, misdiagnosis could easily be made;?The language and cognition improved in most patients who accept steroid therapy;?Our scale can effectively evaluate the prognosis of the patients;?Ketogenic diet could be used as a alternative treatment for some of the refractory LKS. PART2Verification studies of the Genome-wide Copy Number Variations (CNVs) of20patients with Landau-Kleffner syndromeObjective:The etiologies of LKS remain unclear, it was inferred that genetic mechanisms played a role in LKS.The Copy Number Variations (CNVs) can be used to explore the genetic mechanisms of LKS. Our colleagues used SNP chips (Affymetrix Genome-wide SNP Array6.0) to check the CNV in12LKS paitents. The preliminary result showed that there were some dubious CNVs might lead to the cause of LKS, but need further verification. We used high density chip to do comparative genomic hybridization and go on exploring the role of CNV in LKS.Methods:We collected blood samples from20patients and9pair of parents; the DNA was extracted from antieoagulated peripheral blood by using Gentra(?) Puregene(?) Blood Kit; Microarray testing by1×1M and2x400K SurePrint G3Human CGH chips were used. The result was analysis by the software of Agilent Genomic Workbench7.0.4. At last we compared copy number variants with Database of Genomic Variants to search the possible gene which could cause LKS; Review the literature and analyse the function of the gene to find the CNV which may lead to LKS.Result:In19of the20patients, we totally detected81rarely CNVs; including24losses and57gains, the length was from3506to580132bp, the median length was14192bp, the average length was74188bp;3novel CNVs were detected in3patients.Conclusion:Though LKS showed high heterogeneous in heredity, some CNVs still existed in.same area or affected some other genes. The different CNVs may lead to the complex clinical feature of LKS.