Study Of Landau-Kleffner Syndrome With Clinical Features And Genome-wide Copy Number Variations

Part 1Clinical features and therapeutic effecte of 30 patients with Landau-Kleffner syndromeObjective:To study the clinical features, therapeutic effect and prognostic factors in children with Landau-Kleffner syndrome (LKS).Methods:Thirty patients with LKS were enrolled in Children s Hospital of Fudan University from July 2005 to February 2012. Clinical features and electroencephalography results were analyzed retrospectively. All patients were given Corticosteroids treatment for 6 months and some of them had antiepileptic drugs based on their epilepsy seizure type. All patients were followed and long-term outcomes were recorded including language and cognitive development and EEG results. All patients were divided into two groups according to their development outcome. Correlations between high risk factors and outcomes were analyzed with Fisher exact test by SPSS software.Result:1. General data:Thirty patients were enrolled including 13 male and 17 female. Their age ranged from 30 to 168 months (median age 59.5 months). The onset age of aphasia was from 14 to 168 months (median age 43 months). The course form onset to diagnosis was from 10 days to 7 years (median 6 months).2. Clinical features: ①aphasia:There were 8 cases (26.7%) presenting acute onset and 22 cases presenting chronic onset (73.3%). Eleven patinets (36.7%) had expressive aphasia, and 19(63.3%) had both receptive and expressive aphasia. Seventeen patients (56.7%) had complete aphasia and 13 had partial aphasia. ②Epilepsy:Twenty patients had epileptic seizure (66.7%). Among them, sixteen children had epilepsy before aphasia (80%) and four children had seizure after that (20%). Single seizure accounted for 85%(17 cases) and multiple seizures accounted for 15%(3 cases).③Cognitive assessment:Moderate abnormal cognitive function accounted for 64% ④EEG: Seventeen patients (63%) had normal and 10 patients had mild slow background activity. Twenty-eight patients had epileptiform discharges and seven children had electrical status epilepticus during sleep (ESES) (23.3%).3. Prognosis:The follow-up time was 3 weeks in 29 cases,3 months in 28 cases,6 months in 26 cases,12 months in 18 cases,2 years in 9 cases,3 years in 6 cases and more than 3 years in 6 cases. ①aphasia:There were 15 patients (57.7%) totally recovered and 11 patients (42.3%) partially recovery. Other four patients were lost to follow-up. The onset time of treatment was within 3 months in 89.3% patients. The effectual time was within 6 months in 77.3% patients. There were 80% children recovered totally within 1 year. Three patients relapsed.②Epilepsy:Twenty patients had epileptic seizure. Eighteen of them (90%) were controlled for seizure and the other two (10%) improved. ③ Cognitive function:Two thirds of all patients had cognitive dysfunction. ④EEG: Ten patients had slower background initially and returned to normal totally later. Twenty-eight patients had discharges. Up to now epileptiform discharges disappeared in 13 children. All ESES disappeared within 3 weeks, while three patients had recurrent ESES.4. Prognostic factors:Although there was no statistical significance of relationship between all risk factors and outcomes, the data showed the patients who had longer course of disease, presenting aphasia at a younger age and having ESES probably had poor outcomes.Conclusion:LKS is rare, and its clinical features need to be identified further. Corticosteroids treatment was effective. Some patients still had cognitive dysfunction. A few patients had recurrence. The course of disease, onset age of aphasia and ESES might have important impact on long-term outcome.Part 2Study of Genome-wide Copy Number Variations in 12 patients with Landau-Kleffner syndromeObjective:The etiologies of LKS remain unknown. The genetic basis of LKS remains an important topic. Recent advances in high-throughput array-based technology makes it possible to detect several possible DNA sequence variations associated with LKS, including submicroscopic deletions and duplications, also known as Copy Number Variations (CNVs).Methods:Based on precious 12 cases diagnosed as LKS in our hospital, the DNA of cases was extracted from anticoagulated peripheral blood by using TIANgen kit. Microarray testing by CNV affymetrix 6.0 chips was used to detect. The result was entered into the software of Chromosome Analysis Suite (ChAS). Then we compared copy number variants with Database of Genomic Variants.Result:Our preliminary study performed genome-wide copy number variation (CNV) arrays. After excluding smaller gains or loss and the segments which cross centromere, we got 20 chromosome segments that might be significant. Through literature reading, suggested 3p12.3 and Xq21.1 associated with LKS.Conclusion:Our results suggest these CNV may be related to the pathogenesis of LKS.