SCN1A Dravet Syndrome, Epilepsy, Autism and Vaccines ?

Presented at IMFAR 2012.

Dravet Syndrome- Genetic Analysis of SCN1A and PCDH19 Mutations for 17 Chinese Children

V. C. N. Wong, A. K. Y. Kwong and C. W. Fung, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China


Background:   For Dravet syndrome (DS), 80% had mutation in SCN1A gene, which encoded a voltage-gated sodium channel. Recent study demonstrated that 16% of SCN1A-negative patients had mutations in protocadherin-19 (PCDH19) genes.”

Objectives:  The present study examined the genetic mutations in Chinese DS children and assesses the relationship between mutation and phenotype.

Methods:  DNA of 17 DS in The University of Hong Kong was screened for SCN1A mutation using polymerase chain reaction and direct sequencing. SCN1A-negative female patients were then screened for PCDH19 mutation.

Results:  For DS, 82% (14/17) had SCN1A mutations- truncating mutations (6), splice site mutations (2) and missense mutations (6). These mutations affected Nav1.1 protein functions by pathogenicity assessments including conservative, SIFT and Align-GVGD analyses.

We found a relationship between the type of mutation and the degree of intellectual disability (p<0.05), with truncating/ splice site mutations associated with moderate/ severe mental retardation. At the evolution of the disease, 79% (11/14) of DS patients with SCN1A mutations had features which fit into the diagnostic criteria of autism spectrum disorder (ASD). 57% (8/14) had history of vaccination-induced seizures. One of the two female SCN1A-negative patients had PCDH19 mutation.

Conclusions:  High percentage of genetic mutations was identified in our Chinese cohort of Dravet Syndrome. Pathogenicity assessment demonstrated that the mutations were linked to the phenotypes of Dravet syndrome. Our detection of high frequency of ASD (79%) and vaccination-induced encephalopathy (57%) in those DS with SCN1A mutation suggested evaluating ASD with epilepsy or vaccination induced encepalopathic children for any relationship between SCN1A mutations.”

Previous research in May 2012

SCNIA Mutation Associated With Intractable Myoclonic Epilepsy and Migraine Headache.

Mutations in the SCN1A gene are associated with a variety of epilepsy syndromes and more recently with familial hemiplegic migraine. The spectrum of phenotypes can be quite broad even within the same family and with the same mutation. Here we describe a child with intractable myoclonic epilepsy and autism spectrum disorder who carries an inherited mutation in SCN1A (c.3521C>G, p.T1174 S). Previous reports suggest this mutation causes familial hemiplegic migraine and interestingly both the patient’s mother, who also carries the mutation, and the patient’s maternal grandmother, have frequent migraines with aura.

Sodium channels SCN1A, SCN2A and SCN3A in familial autism.

Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.

De novo mutations revealed by whole-exome sequencing are strongly associated with autism.

Dravet syndrome: patients with co-morbid SCN1A gene mutations and mitochondrial electron transport chain defects.

Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.

Epilepsy and the new cytogenetics.

Genetic calcium signaling abnormalities in the central nervous system: seizures, migraine, and autism.

[Autism, epilepsy and genetics]. Spanish Original

This entry was posted in Autism, co-morbid, epilepsy, Genetics, Neurology, Treatment, Uncategorized. Bookmark the permalink.

3 Responses to SCN1A Dravet Syndrome, Epilepsy, Autism and Vaccines ?

  1. Catherina says:

    “vaccination-induced encephalopathy”

    is a misleading term in Dravet Syndrome. There has been research (e.g to show that long term course of disease in Dravet Syndrome is not different between children whose first seizure had been triggered by vaccination vs those whose first seizure was caused by another stimulus (a warm bath or exciting doctor’s visit can be enough – neurons with a mutated sodium channel just do not function normally).

  2. Catherina thank you for your valuable post. It reminds the reader and myself that both epilepsy and autism are complex, as is the interplay of genes.

  3. A retrospective study of the relation between vaccination and occurrence of seizures in Dravet syndrome.

    Department of Neuropediatrics, BHZ Vogtareuth, Epilepsy Center, Vogtareuth, Germany.

    Dravet syndrome is a severe epileptic encephalopathy starting in the first year of life. Mutations in SCN1A can be identified in the majority of patients, and epileptic seizures in the setting of fever are a clinical hallmark. Fever is also commonly seen after vaccinations and provocation of epileptic seizures by vaccinations in patients with Dravet syndrome has been reported, but not systematically assessed. In a retrospective evaluation of 70 patients with Dravet syndrome and SCN1A mutations, seizures following vaccinations were reported in 27%. In 58% of these patients vaccination-related seizures represented the first clinical manifestation. The majority of seizures occurred after DPT vaccinations and within 72 h after vaccination. Two-thirds of events occurred in the context of fever. Our findings highlight seizures after vaccinations as a common feature in Dravet syndrome and emphasize the need for preventive measures for seizures triggered by vaccination or fever in these children.

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