When to Suspect Dravet Syndrome?
In 2022, an international consensus panel of experts on the diagnosis and treatment of Dravet syndrome was published. This was created due to the recently approved specific treatments for this disease and the development of disease-modifying therapies. The goal of the consensus is to improve diagnosis, set therapeutic goals, and optimal treatment procedures. We summarize the symptoms of the disease and situations in which genetic testing of the causal mutation is appropriate.
Dravet Syndrome
Dravet syndrome (DS) is a developmental epileptic encephalopathy beginning in early childhood, characterized by lifelong occurrence of seizures resistant to therapy and associated disorders of intellect, behavior, sleep, and gait. The vast majority of cases are due to a pathogenic variant of the SCN1A gene, leading to haploinsufficiency of the sodium channel α-subunit.1
Clinical Manifestations
Seizures in Children
The first seizure in a previously healthy child appears by 19 months of age. It is initially usually triggered by fever or overheating, but over time, afebrile seizures occur, which can be triggered by emotional stress, excitement, or flashing lights. Types of seizures include hemiclonic, generalized tonic-clonic, myoclonic, absence, focal with impaired awareness, sometimes tonic. Prolonged seizures, seizure clusters, and convulsive or non-convulsive status epilepticus (SE) can also occur.2 More than half of patients exhibit myoclonic and focal seizures with impaired awareness by age 5.1
Seizures in Adults
With increasing age, the occurrence of epileptic seizures, SE, and fever sensitivity decreases. Some types of seizures may disappear entirely, and many adults have sleep-related seizures. Nevertheless, polytherapy remains necessary, and severe epilepsy with convulsive and non-convulsive SE is present.2 Most adults continue to experience short generalized tonic-clonic seizures.1
Intellectual Disability
The majority of adult patients exhibit moderate to severe intellectual disability. Deterioration or loss of previously acquired skills often occurs after a severe seizure or SE. Some patients have been reported to have autism.
Behavioral Disorders
Children exhibit attention deficits, agitation, irritability, and aggression. In adults, there is a calming effect, but social connections and adaptive behavior may be disrupted by intellectual disability or autistic traits.
Gait, Motor, and Bone Disorders
Adolescents and adults display hunched posture, dystonic ataxic gait with a broad base, or parkinsonian gait. Older patients commonly exhibit parkinsonism symptoms such as bradykinesia, asymmetric rigidity, etc. Kyphosis or kyphoscoliosis may be present.2
When Genetic Testing is Appropriate
The diagnosis of DS made based on clinical presentation can be confirmed by genetic testing for mutations in the SCN1A gene.
According to the 2022 international consensus panel of experts on the diagnosis and treatment of Dravet syndrome, genetic testing for the SCN1A mutation is appropriate for developmentally normal children who, between the ages of 2 and 15 months, have a single prolonged hemiclonic seizure (5–29 minutes) or focal/generalized SE (≥ 30 minutes) of unknown etiology in association with vaccination or fever.
The expert panel also recommends testing children aged 2–15 months with recurrent prolonged focal or generalized convulsive seizures of unknown etiology with or without fever (including SE), and children aged 6–15 months experiencing recurrent short hemiclonic seizures without fever.1
Results of Other Examinations
A pathogenic variant of the SCN1A gene is found in > 85% of cases. Initial MRI findings are generally normal, but some patients may exhibit various degrees of cortical atrophy and hippocampal sclerosis. EEG is often normal up to 12 months of age, but by age 5, most cases show slowing of background activity and epileptiform discharges.1
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Sources:
1. Wirrell E. C., Hood V., Knupp K. G. et al. International consensus on diagnosis and management of Dravet syndrome. Epilepsia 2022; 63 (7): 1761–1777, doi: 10.1111/epi.17274.
2. Andrade D. M., Berg A. T., Hood V. et al. Dravet syndrome: a quick transition guide for the adult neurologist. Epilepsy Res 2021; 177: 106743, doi: 10.1016/j.eplepsyres.2021.106743.
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