Autism In Febrile Seizures Related Epilepsy: Prevalence, Features, And Relationship To The Clinical Characteristics Of Epilepsy, Mental Retardation And SCN1A Mutation

Purpose To study autism in febrile seizures related epilepsy: prevalence, features, and relationship to the clinical characteristics of epilepsy, mental retardation and SCN1A mutation.Methods The patients were recruited from 6040 epilepsy patients (including 2033 children) visiting our hospital's Epilepsy Center between 1997 and 2008. According to the criteria of the Commission on Classification and Terminology of the International League Against Epilepsy (ILAE) (1981, 1989), FS, Dravet syndrome(DS), MAE were diagnosed; according to international criteria, GEFS+, SMEB were diagnosed,and the diagnosis of PEFS+ was made based on the partial seizures. Autism was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and the International Classification of Diseases, 10th edition(ICD-10). The Autism Behavior Checklist (ABC) was completed, as a screening tool, by the parents under the supervision of a psychiatrist, and the Childhood Autism Rating Scale (CARS) by a psychiatrist for assistance in diagnosis. For evaluation of mental retardation, the Chinese Wechsler Intelligence Scale for Children (C-WISC) was administered by qualified psychologists to the children aged 6 years or above. Gesell Developmental Scales were used for the children less than 6 years old. Clinical data were collected, including the onset age of seizures, family history, seizure types and frequency, neurological examination, and response to anti-epileptic drugs (AEDs). Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) were performed. DNA of the febrile related epilepsy patients were extracted from peripheral blood. All exons of SCN1A gene were screened with denaturing high performance liquid chromatography (DHPLC) technology, and then sequence analysis was performed on those with abnormal elution peak.Result One hundred and three patients were studied, among them there were 39 (25male) patients with GEFS+, 26 (16 male) patients with PEFS+, 37 (27 male) patients with DS (14 SMEI and 23 SMEB) and 1 patient with MAE (male). Forty-two patients (40.8%) had family history of febrile seizures or epilepsy. Seizure types were multiple, generalized seizures included GTCS, myoclonic, absence, tonic and atonic seizures; partial seizures included CPS, SPS, sGTCS and unilateral clonic seizures. GTCS occurred in 94.9% of patients with GEFS+, CPS in 88.5% of patients with PEFS+, SPS in 23.1% of patients with PEFS+; and in patients with DS, GTCS (86.5%, including secondary GTCS) and complex partial seizures (59.5%) were the most common seizure types. Status epilepticus (SE) occurred in 70.3% of patients with DS. All of 11 patients were diagnosed with autism, including 9 autism disorder and 2 PDD-NOS. One (2.6%) patient with GEFS+, one (3.8%) patient with PEFS+ and 9 (24.3%) patients with DS (4 SMEI and 5 SMEB) were diagnosed with autism. In DS, all patients with autism showed speech delay, no emotional reciprocity, and narrow interest, whereas speech delay, short temper, and narrow interest, respectively, appeared in 89.3%, 46.4%, and 39.9% of patients without autism. IQ/DQ was obtained from all 103 patients, 1 MAE was normal, 46.2% GEFS+ and 30.8% PEFS+ were normal, the remaining of GEFS+ and PEFS+ showed MR; only 2 patients with DS (one with autism and one without autism) showed borderline MR, 94.6% of patients with DS showed MR. Patients with DS with autism had a higher proportion of profound MR, and patients without autism had a higher percentage of mild and moderate MR. SCN1A gene was screened in 103 patients, 8 mutations were found in patients with GEFS+, the percentage of mutation was 20.5%, 8 mutations in patients with PEFS+, the percentage was 30.8%, 15 mutations in patients with DS, the percentage was 40.5%. No mutation was found in the patient with MAE. One SCN1A mutation was found in one patient with PEFS+ with autism. Among 15 patients with DS with SCN1A mutation, there were 5 patients with autism, and 22 patients with DS without SCN1A mutation, there were 4 patients with autism, there was no statistical deference between these two groups. Among 15 patients with DS with SCN1A mutation, 3 patients with autism (60% in patients with autism) had profound MR, 8 patients without autism (80% in patients without autism) had mild to moderate MR.Conclusions The relationship between autism, PEFS+ and SCN1A mutation is still unclear. Although the current understanding of the association between autism and DS is limited, the high prevalence of autistic behaviors in DS suggests a need for clinical attention. Besides the treatment of epilepsy, measures for psychological intervention should be considered. Patients with DS with autism exhibit more severe mental retardation. DS and autism might share the common molecular mechanisms ----SCN1A mutation. Further clinical studies with large sample sizes and basic research on the underlying pathogenesis mechanism are needed.