Autism in Dravet syndrome: Prevalence, features, and relationship to the clinical characteristics of epilepsy and mental retardation

doi:10.1016/j.yebeh.2011.04.060

Epilepsy & Behavior

Volume 21, Issue 3, July 2011, Pages 291-295

https://doi.org/10.1016/j.yebeh.2011.04.060 Get rights and content

Abstract

Autism is a pervasive developmental disorder that frequently co-occurs with epilepsy. Dravet syndrome is a severe epileptic encephalopathy associated with psychomotor developmental delay. Autism in Dravet syndrome, however, has rarely been studied. In this study, the prevalence and features of autism in patients with Dravet syndrome, their potential association with mental retardation, and the clinical characteristics of epilepsy were investigated. Clinical data of 37 patients with Dravet syndrome were collected, and evaluations of autism and mental retardation were performed. Nine patients (24.3%) met the criteria for autism. All patients with autism showed speech delay, no emotional reciprocity, and narrow interests, whereas 89.3, 46.4, and 39.9% of patients without autism had speech delay, short temper, and narrow interests, respectively. Mental retardation was observed in 94.6% of patients with Dravet syndrome, with more frequent severe or profound mental retardation in those with autism. The clinical features of epilepsy did not statistically differ between the patients with autism and the patients without autism.

Research highlights

► The prevalence and features of autism in patients with Dravet syndrome are assessed. ► The majority of patients with Dravet syndrome exhibit some symptoms of autistic spectrum disorder. ► Patients with Dravet syndrome with autism exhibit more severe mental retardation. ► This is the first clinical study demonstrating autism in Dravet syndrome.

Introduction

Autism is a developmental disorder that is diagnosed on behavioral criteria in three domains: stereotypical behaviors, social interactions, and verbal and nonverbal communication. About one-third of individuals with autism develop seizures sometime in life [1]. A conservative estimate of epilepsy in autism is approximately 25% [2], and Matsuo and colleagues found that 15.2% of their epilepsy cases were complicated by autistic spectrum disorder (ASD) [3], suggesting a close relationship between autism and epilepsy. The prevalence of autism may differ in some syndromes associated with epilepsy, and has been estimated to be especially high in some diseases, such as tuberous sclerosis [4]. Unfortunately, there is a lack of data on autism in the majority of epileptic syndromes and further research is needed.

Dravet syndrome (DS), also called severe myoclonic epilepsy in infancy (SMEI), is a typical refractory epileptic encephalopathy [5]. The incidence of DS is relatively low, estimated to be about 1 per 40,000 children. It affects males twice as often as females [6]. DS is characterized by febrile or afebrile generalized tonic–clonic seizure (GTCS) and often prolonged unilateral or generalized clonic seizures occurring from the first year of life in an otherwise normal infant. The patient may experience multiple seizure types later. Patients with DS usually carry a high risk of mental retardation (MR) and behavioral disorders after age 2 [7], sometimes accompanied by psychotic or autistic traits and hyperactivity [8]. However the prevalence and clinical features of autism in DS have not been well clarified. This study evaluated autistic behaviors in children with DS and analyzed the potential relationships of autism to MR and other clinical characteristics of DS.

Section snippets

Methods

A total of 41 children (31 boys, 10 girls) with DS were recruited from 6040 patients with epilepsy (including 2033 children) in our hospital's Epilepsy Center between 1997 and 2008. Patients were followed more than 2 years (range: 2–6). Four patients were unavailable for follow-up. Clinical data collected included age at onset of seizures, family history, seizure types and frequency, neurological examination results, and response to antiepileptic drugs (AEDs). Brain MRI scans and EEGs were

Demographic and clinical characteristics of patients with Dravet syndrome

Demographic and clinical features of the 37 patients with Dravet syndrome are summarized in Table 1. Patients ranged in age from 4.1 to 15.8 years (mean = 9.3). All patients were born in good condition after uneventful pregnancies.

All of the patients experienced two or more types of seizures, including generalized tonic–clonic (GTCS), atypical absence, and myoclonic, partial, tonic, or atonic seizures. GTCS (including secondarily GTCS), complex partial seizures, and status epilepticus were quite

Discussion

The frequency and clinical features of autism in patients with Dravet syndrome were assessed in this study. Of the cases of DS, 24.3% were complicated by autism, and most of the remaining patients showed some ASD symptoms (especially speech delay, short temper, and narrow interests). The patients with autism and DS also had more severe MR. Although the current understanding of the association between autism and DS is limited, the relationship reveals the importance and necessity of further

Ethical approval

We confirm that we have read the Journal's position on issues involved in the ethical publication and affirm that this report is consistent with those guidelines.

Conflict of interest statement

We have no conflicts of interest to disclose.

Acknowledgments

The authors thank Dr. Xiao-Bing Zou and Dr. Chun Tang from the Third Affiliated Hospital of Sun Yet-San University for confirming autism diagnoses. The authors also thank Dr. Bin Zhang for data analysis and statistical help. This study was supported by the National Nature Science Foundation of China (No. 30700247, Xiao-Rong Liu) and by Doctor/Overseas Personnel Startup Funding from Guangzhou Medical University PRC (No. 2008c14, Bing-Mei Li).

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Citation Excerpt :
SCN1A mutations or deletions are implicated in up to 80% of cases.72 Most children with DS exhibit autistic features,73 which become apparent between the ages of 1 year and 4 years in parallel with slowing or static psychomotor development.74 Approximately 50% of patients meet diagnostic criteria for autism,31 in a majority of cases in conjunction with profound ID.73

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¹: Co-first author.

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Autism in Dravet syndrome: Prevalence, features, and relationship to the clinical characteristics of epilepsy and mental retardation

Abstract

Research highlights

Introduction

Section snippets

Methods

Demographic and clinical characteristics of patients with Dravet syndrome

Discussion

Ethical approval

Conflict of interest statement

Acknowledgments

Epilepsy Behav

Lancet Neurol

Brain Dev

Lancet Neurol

Brain Dev

Brain Dev

Epilepsy Res

Brain Dev

Biol Psychiatry

Brain Dev

Autism and tuberous sclerosis

J Child Neurol

Proposal for revised classification of epilepsies and epileptic syndromes

Epilepsia

Epidemiology of severe myoclonic epilepsy of infancy

Epilepsia