Dravet Syndrome: The Fever-Triggered Epilepsy of Infancy

Table of Contents

  1. What Dravet Syndrome Is
  2. How Common It Is
  3. The SCN1A Gene and the Brain's Braking Cells
  4. How It Differs From Ordinary Febrile Seizures
  5. How the Condition Changes Over the Years
  6. Status Epilepticus, SUDEP and Early Death
  7. How the Diagnosis Is Made
  8. What the Research Found About Vaccination
  9. Medicines Tested in Dravet Syndrome Trials
  10. Medicines Reported to Worsen Seizures
  11. Gene-Targeted Treatment in Trials
  12. What Is Not Known
  13. Key Research Papers
  14. Other Sources
  15. Connections
  16. Featured Videos

What Dravet Syndrome Is

Dravet syndrome is a rare and severe form of epilepsy that begins in the first year of life. Doctors call it a developmental and epileptic encephalopathy: a condition in which the seizures and the underlying brain disorder together slow a child's development. Its older name, used in many of the founding studies, was severe myoclonic epilepsy of infancy. The syndrome is named after the physician Charlotte Dravet, a co-author of two of the studies cited on this page.

The typical story, as the research describes it, starts with a baby who has been developing normally. Somewhere in the first year, often during a fever, the baby has a long convulsive seizure — sometimes affecting one side of the body, sometimes the whole body. More seizures follow, frequently long ones, and frequently set off by fever again. A 2001 genetics paper summed up the early picture: generalized tonic, clonic and tonic-clonic seizures that are first induced by fever and begin during the first year of life, followed later by other seizure types, with development that stagnates around the second year.

Most cases are caused by a change in one gene, SCN1A, that has arisen new in the child rather than being inherited. The seizures are hard to control with ordinary epilepsy medicines, and some ordinary epilepsy medicines make them worse. Since 2000, and mostly since 2017, randomised trials have tested medicines specifically in Dravet syndrome, and in 2026 the first results of a gene-targeted treatment were published.

For seizures and epilepsy in general, see the site's Epilepsy page. For the common, usually harmless seizures many young children have with a fever, see Febrile Seizures.

How Common It Is

Dravet syndrome was long described in the United States as affecting about 1 in 40,000 children. A 2015 study tested that figure in a whole birth population for the first time since genetic testing became routine. Researchers looked at every infant born in a large Northern California health system from 2007 to 2010 who had two or more seizure diagnoses before 12 months of age and was still on epilepsy medicine at 24 months. A child neurologist then checked each record against five features of the syndrome:

Eight infants met the criteria, which works out to about 1 in 15,700 births. Six of them had a new (de novo) SCN1A change likely to cause disease, an incidence of about 1 in 20,900. All 8 had seizures with fever, and 6 had seizures lasting longer than 10 minutes by their first birthday. The authors concluded that Dravet syndrome caused by SCN1A is about twice as common in the United States as earlier estimates suggested.

The SCN1A Gene and the Brain's Braking Cells

Nerve cells fire electrical signals by opening tiny pores, called sodium channels, that let sodium rush in. The SCN1A gene carries the instructions for one of these channels, known as Nav1.1. (The site's Nerve Impulse animation shows how sodium entry drives a nerve signal.)

In 2001 a research team examined seven unrelated children with severe myoclonic epilepsy of infancy and found an SCN1A mutation in every one of them: four frameshift mutations, one nonsense mutation, one splice-site mutation and one missense mutation. All seven were de novo — present in the child but not the parents — and none were found in 184 control chromosomes. Milder SCN1A changes had already been found in families with a milder inherited condition called generalized epilepsy with febrile seizures plus, which is why the team looked at this gene.

Most of the mutations in that first paper would be expected to break the channel. That raised a puzzle: if the brain has fewer working sodium channels, why would it become more prone to seizures? A 2006 study in mice gave the leading answer. In mice missing one copy of the Scn1a gene, the sodium current was sharply reduced in the brain's inhibitory interneurons — the cells that release gamma-aminobutyric acid (GABA) and act as the brain's brakes — but not in the excitatory pyramidal cells. The mice had spontaneous seizures and sporadic deaths. The authors proposed that weak braking cells, rather than overactive firing cells, cause the overexcitement that leads to seizures in children with the syndrome. The site's GABA animation and What Happens in a Seizure animation illustrate this balance between brakes and accelerator.

Later papers describe Dravet syndrome as caused primarily by SCN1A haploinsufficiency — one working copy of the gene not making enough channel on its own. That idea is the basis of the gene-targeted treatment described further down this page.

How It Differs From Ordinary Febrile Seizures

Seizures with fever are common in young children, and the great majority are febrile seizures that the child outgrows with no lasting harm. The Febrile Seizures page covers that much larger group. Dravet syndrome is rare, but it also starts with seizures during fever, which is why studies list features that set it apart. In the research cited here, those features are:

Fever is the classic trigger, but the long-term study from Marseille describes sensitivity to temperature changes in general that lasts through life, though its effect becomes milder than in infancy. The same study reported photosensitivity and pattern sensitivity (seizures set off by flashing lights or patterns) that tended to fade before age 20.

How the Condition Changes Over the Years

The seizures and the developmental effects of Dravet syndrome follow different paths over time. Research describes seizures that become less frequent after early childhood, while learning, behaviour and movement problems become more obvious.

Development, behaviour and autism features

A UK study followed children with SCN1A-positive Dravet syndrome for 10 years, from 2010 to 2020, using caregiver questionnaires (68 of 113 caregivers returned them). Average developmental scores moved from the moderate to the profound range of cognitive impairment over the decade, while epilepsy severity appeared somewhat less severe at follow-up. Other problems became more common over the same period:

Poorer language at the start, more severe epilepsy at the start and a more damaging SCN1A variant each predicted a worse developmental outcome. More than 90% of caregivers reported harm to their own health and work opportunities.

Movement and walking

A 2011 report from the Centre Saint-Paul in Marseille followed 24 people with the syndrome up to age 50. Signs from the cerebellum (the brain's balance centre) — unsteadiness, slurred speech, tremor on movement and eye-movement problems — became more prominent with age. Walking was markedly impaired, often because of orthopaedic problems such as a curved spine (kyphosis or kyphoscoliosis), flat feet or claw feet. These problems were minor in childhood and worsened during and after adolescence, despite physiotherapy.

Seizures in adulthood

In the same group, seizures became less frequent and less severe after childhood. Generalized convulsive seizures were the one seizure type seen in almost all adults, mostly at night. Myoclonic seizures, atypical absences and focal seizures were uncommon in adulthood. Only 3 of the 24 adults lived independently.

Sleep

A 2025 Italian study notes that sleep disorders are reported in up to 85% of people with Dravet syndrome. Its overnight sleep recordings in 30 patients with a confirmed SCN1A variant found that seizures during sleep were linked with less deep (slow-wave) sleep and, for tonic seizures, less dreaming (REM) sleep. The authors suggested that disturbed deep sleep may be one of the ways the disorder affects the brain over time, and observed that patients taking fenfluramine seemed to have more stable sleep.

Status Epilepticus, SUDEP and Early Death

Dravet syndrome carries a higher risk of early death than most epilepsies. The two main dangers in the research are status epilepticus — a seizure that does not stop on its own — and sudden unexpected death in epilepsy (SUDEP), in which a person with epilepsy dies suddenly with no other cause found.

Status epilepticus

The International League Against Epilepsy (ILAE) defines convulsive status epilepticus using two time points. After 5 minutes, a convulsive seizure is regarded as continuous seizure activity, the point at which hospitals treat it as an emergency. After 30 minutes, there is a risk of long-term consequences such as nerve-cell injury. The ILAE describes these times as the best estimates currently available.

A 2023 study of 510 people with genetic developmental and epileptic encephalopathies found that convulsive status epilepticus was most common in SCN1A-related conditions: 181 of 203 people with Dravet syndrome (89%) had had at least one episode.

A 2017 report described five children with Dravet syndrome and de novo SCN1A mutations who developed severe brain swelling after status epilepticus with fever, and died. All had a measured fever of 40 °C or higher. In four of them, signs of brainstem compression first appeared 3 to 5 days after they came to hospital; in one, as early as 24 hours. The authors described this brain swelling as a previously unreported complication that may contribute to early deaths in the syndrome. The report cites a mortality of 15% by age 20 in Dravet syndrome.

SUDEP and overall mortality

A 2016 cohort followed 100 consecutive, unrelated people with Dravet syndrome, 87 of whom had SCN1A mutations; living patients had a median follow-up of 17 years. Seventeen died, at a median age of 7 years. The causes were:

The death rate was 15.84 per 1,000 person-years and the SUDEP rate 9.32 per 1,000 person-years. The authors noted this is considerably higher than a reported 5.1 per 1,000 person-years for adults with drug-resistant epilepsy, and that SUDEP in Dravet syndrome happens mainly in childhood.

A 2016 review gathered 177 published deaths. SUDEP was the likely cause in 87 (49%), status epilepticus in 56 (32%), drowning or accidents in 14 (8%) and infections in 9 (5%). Of the 142 deaths with a recorded age, 73% happened before age 10. In the Marseille adult follow-up, 5 of 24 patients (20.8%) died, at an average age of 24.8 years — three from SUDEP, one from status epilepticus and one from an unknown cause.

The UK 10-year study found that SUDEP had not been discussed with a medical professional for 35% of the families who answered.

How the Diagnosis Is Made

The diagnosis of Dravet syndrome rests on the pattern of seizures over time and on genetic testing.

In 2022 a 31-member international expert panel, shaped by both physicians and caregivers, reached consensus through a structured process called a Delphi survey. There was strong agreement that infants aged 2 to 15 months who have either a first prolonged hemiclonic seizure or a first convulsive status epilepticus, with fever or following vaccination, and no other explanation, are candidates for genetic testing for Dravet syndrome. The 2015 population study authors had earlier proposed considering genetic testing in children with two or more prolonged febrile seizures by 1 year of age.

A genetic result does several things. It can confirm the diagnosis earlier than waiting for the full clinical picture to unfold. It points away from medicines known to worsen seizures in this syndrome. And, as the next section describes, it changed how one class of supposed vaccine injuries was understood. A positive SCN1A test does not settle everything: SCN1A changes are also found in milder conditions, and not every child with Dravet syndrome has an identified SCN1A change (13 of the 100 patients in the 2016 mortality cohort did not).

What the Research Found About Vaccination

For decades some children were described as having vaccine encephalopathy: a child developing normally had a first seizure shortly after a vaccination, then went on to severe epilepsy and intellectual impairment. Pertussis (whooping cough) vaccination in particular was blamed. Two studies with overlapping authors, published four years apart, tested this.

Berkovic and colleagues, 2006

The team re-examined 14 people with alleged vaccine encephalopathy whose first seizure came within 72 hours of a vaccination. Eleven of the 14 carried an SCN1A mutation, and a specific epilepsy syndrome was diagnosed in all 14. In all nine cases where the parents' DNA was available, the mutation had arisen de novo. Every one of the 8 patients whose features matched severe myoclonic epilepsy of infancy had a mutation. The authors concluded that cases of alleged vaccine encephalopathy could in fact be a genetically determined epileptic encephalopathy that arose de novo.

McIntosh and colleagues, 2010

The follow-up study answered the next question: does a vaccine-timed start change how a child with Dravet syndrome ends up? Among 40 patients with SCN1A mutations and source records, there was a cluster of first seizures within 2 days after vaccination. Children whose seizures began on the day of or the day after vaccination (12 children) had their first seizure at an average of 18.4 weeks, compared with 26.2 weeks in the other 28 children — about 7.8 weeks earlier. But there were no differences in intellectual outcome, later seizure types or type of mutation between the two groups. In a further analysis, intellectual outcome did not differ between children who received vaccinations after their seizures began and those who did not.

The authors wrote that vaccination might trigger earlier onset in children who, because of an SCN1A mutation, are destined to develop the disease, and concluded that “vaccination should not be withheld from children with SCN1A mutations” because they found no evidence that vaccinations before or after onset affect outcome.

The site's Genetic Susceptibility to Vaccine Adverse Reactions page places these two studies in the wider question of which children are susceptible to rare vaccine reactions, and what testing exists.

Medicines Tested in Dravet Syndrome Trials

Three medicines have been tested in randomised placebo-controlled trials designed specifically for Dravet syndrome, and each was added on top of the medicines the children were already taking. The trials below are reported as published; figures are the trials' own. The 2022 international consensus reported agreement on first- to third-line maintenance treatments that include these newer medicines. Decisions about epilepsy medicines belong with the treating neurologist.

Stiripentol

The trial report describes stiripentol as an inhibitor of cytochrome P450, a family of liver enzymes that break down many other medicines. The 2000 French STICLO trial enrolled 41 children with severe myoclonic epilepsy of infancy who were already taking valproate and clobazam. Over two months:

The current United States label covers seizures of Dravet syndrome in patients taking clobazam who are 6 months or older and weigh at least 7 kg, and states there are no clinical data on stiripentol used alone. The label reports drowsiness in 67% of stiripentol-treated patients in the controlled studies, compared with 23% on placebo, and lists reduced appetite and weight loss, and low white-cell and platelet counts, with blood counts taken before treatment and every 6 months.

Cannabidiol

Cannabidiol is a compound from the cannabis plant, tested in these trials as a pharmaceutical oral solution. In the 2017 trial, 120 children and young adults with drug-resistant Dravet syndrome received 20 mg per kg of body weight per day or placebo for 14 weeks:

A second trial, published in 2020, compared 10 and 20 mg per kg per day with placebo in 198 children aged 2 to 18. Convulsive seizures fell by 48.7% with the lower dose and 45.7% with the higher dose, compared with 26.9% on placebo. Raised liver enzymes occurred in 13 children on the higher dose and 3 on the lower dose, all of them also taking valproate. The authors reported a better safety profile at the lower dose.

The United States label lists hepatic injury as a warning and calls for liver transaminase (ALT and AST) and bilirubin tests in all patients before starting. In the controlled studies, ALT rose above three times the upper limit of normal in 13% of cannabidiol-treated patients compared with 1% on placebo, and most of these rises occurred in patients also taking valproate. The label covers patients 1 year and older.

Fenfluramine

Fenfluramine acts on the brain's serotonin system. It was once sold as an appetite-suppressing weight-loss drug and was withdrawn in 1997 after reports of heart-valve disease. It has since been studied at much lower doses for Dravet syndrome.

In the 2019 trial, 119 children and young adults (average age 9) were randomly assigned to placebo or to fenfluramine 0.2 or 0.7 mg per kg per day for 14 weeks:

A 2020 trial tested fenfluramine 0.4 mg per kg per day in 87 children whose seizures were not controlled on regimens that included stiripentol. Monthly convulsive seizures fell 54.0% more than on placebo, and 54% of children on fenfluramine had at least a halving of seizures, compared with 5% on placebo.

In the long-term open-label extension, 327 patients were followed with echocardiograms every 3 months for a median of 23.9 months; no patient developed valvular heart disease or pulmonary arterial hypertension.

The United States label nonetheless carries a boxed warning that fenfluramine can cause valvular heart disease and pulmonary arterial hypertension. It requires echocardiograms before, during and after treatment, and restricts the medicine to a special safety programme (a Risk Evaluation and Mitigation Strategy). The label also lists sleepiness, serotonin syndrome when combined with other serotonin-acting drugs, raised blood pressure and glaucoma among its warnings, and covers patients 2 years and older. The site's Pulmonary Arterial Hypertension page describes that lung condition.

A warning shared by all three labels

Each label warns that stopping the medicine suddenly can raise seizure frequency and cause status epilepticus, and states that it is withdrawn gradually.

Medicines Reported to Worsen Seizures

Some widely used epilepsy medicines work by blocking sodium channels — the same kind of channel that is already in short supply in Dravet syndrome. Studies report that some of them make seizures worse in this syndrome rather than better.

The clearest early evidence came from a 1998 study of 21 patients with severe myoclonic epilepsy of infancy, aged 2 to 18, treated with lamotrigine, a sodium-channel-blocking drug:

The authors concluded that the worsening was not explained by the natural course of the disease and that lamotrigine treatment seems inappropriate in this syndrome. A review by the same group that year listed carbamazepine, another sodium-channel blocker, among the drugs reported to cause paradoxical worsening of seizures in children, and repeated that lamotrigine is inappropriate in severe myoclonic epilepsy.

Gene-Targeted Treatment in Trials

Every medicine above treats seizures. Researchers are now testing treatments meant to correct the underlying shortage of the Nav1.1 channel — what papers call disease-modifying treatment.

The first published clinical results concern zorevunersen, an antisense oligonucleotide: a short, man-made strand of genetic material designed to make the healthy copy of SCN1A produce more Nav1.1 channel. It is given by injection into the fluid around the spinal cord (a lumbar puncture). In two open-label phase 1–2a studies published in 2026, 81 patients aged 2 to 18 who were already on standard medicines received one to three doses, and 75 continued in extension studies with a dose every 4 months:

These were open-label studies with no placebo group, so they cannot show how much of the change was caused by the treatment. The authors described the results as supporting further development of zorevunersen as a potential disease-modifying treatment. The 2022 consensus panel agreed in principle on using disease-modifying treatments if they prove safe and effective, but caregivers were more cautious than physicians about when to start them.

What Is Not Known

Key Research Papers

  1. Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet. 2001;68(6):1327-1332. PubMed PMID: 11359211
  2. Yu FH, Mantegazza M, Westenbroek RE, Robbins CA, Kalume F, Burton KA, et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci. 2006;9(9):1142-1149. PubMed PMID: 16921370
  3. Wu YW, Sullivan J, McDaniel SS, Meisler MH, Walsh EM, Li SX, Kuzniewicz MW. Incidence of Dravet Syndrome in a US Population. Pediatrics. 2015;136(5):e1310-e1315. PubMed PMID: 26438699
  4. Wirrell EC, Hood V, Knupp KG, Meskis MA, Nabbout R, Scheffer IE, et al. International consensus on diagnosis and management of Dravet syndrome. Epilepsia. 2022;63(7):1761-1777. PubMed PMID: 35490361
  5. Berkovic SF, Harkin L, McMahon JM, Pelekanos JT, Zuberi SM, Wirrell EC, et al. De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study. Lancet Neurol. 2006;5(6):488-492. PubMed PMID: 16713920
  6. McIntosh AM, McMahon J, Dibbens LM, Iona X, Mulley JC, Scheffer IE, Berkovic SF. Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study. Lancet Neurol. 2010;9(6):592-598. PubMed PMID: 20447868
  7. Genton P, Velizarova R, Dravet C. Dravet syndrome: the long-term outcome. Epilepsia. 2011;52 Suppl 2:44-49. PubMed PMID: 21463279
  8. Feng T, Makiello P, Dunwoody B, Steckler F, Symonds JD, Zuberi SM, et al. Long-term predictors of developmental outcome and disease burden in SCN1A-positive Dravet syndrome. Brain Commun. 2024;6(1):fcae004. PubMed PMID: 38229878
  9. Cossu A, Proietti J, Ghobert L, Rinaldi L, Dalla Bernardina B, Darra F, Cantalupo G. Seizures influence sleep macrostructure and the sleep-wake circadian rhythm in Dravet syndrome. Epilepsia. 2025;66(9):3269-3281. PubMed PMID: 40347411
  10. Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515-1523. PubMed PMID: 26336950
  11. Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE. Rates of Status Epilepticus and Sudden Unexplained Death in Epilepsy in People With Genetic Developmental and Epileptic Encephalopathies. Neurology. 2023;100(16):e1712-e1722. PubMed PMID: 36750385
  12. Myers KA, McMahon JM, Mandelstam SA, Mackay MT, Kalnins RM, Leventer RJ, Scheffer IE. Fatal Cerebral Edema With Status Epilepticus in Children With Dravet Syndrome: Report of 5 Cases. Pediatrics. 2017;139(4):e20161933. PubMed PMID: 28330972
  13. Cooper MS, Mcintosh A, Crompton DE, McMahon JM, Schneider A, Farrell K, et al. Mortality in Dravet syndrome. Epilepsy Res. 2016;128:43-47. PubMed PMID: 27810515
  14. Shmuely S, Sisodiya SM, Gunning WB, Sander JW, Thijs RD. Mortality in Dravet syndrome: A review. Epilepsy Behav. 2016;64(Pt A):69-74. PubMed PMID: 27732919
  15. Chiron C, Marchand MC, Tran A, Rey E, d'Athis P, Vincent J, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group. Lancet. 2000;356(9242):1638-1642. PubMed PMID: 11089822
  16. Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020. PubMed PMID: 28538134
  17. Miller I, Scheffer IE, Gunning B, Sanchez-Carpintero R, Gil-Nagel A, Perry MS, et al. Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome: A Randomized Clinical Trial. JAMA Neurol. 2020;77(5):613-621. PubMed PMID: 32119035
  18. Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10216):2243-2254. PubMed PMID: 31862249
  19. Nabbout R, Mistry A, Zuberi S, Villeneuve N, Gil-Nagel A, Sanchez-Carpintero R, et al. Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial. JAMA Neurol. 2020;77(3):300-308. PubMed PMID: 31790543
  20. Lai WW, Galer BS, Wong PC, Farfel G, Pringsheim M, Keane MG, Agarwal A. Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: Analysis of an ongoing long-term open-label safety extension study. Epilepsia. 2020;61(11):2386-2395. PubMed PMID: 32809271
  21. Agarwal A, Farfel GM, Gammaitoni AR, Wong PC, Pinto FJ, Galer BS. Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: Findings from serial echocardiographic assessments. Eur J Paediatr Neurol. 2022;39:35-39. PubMed PMID: 35640431
  22. Guerrini R, Dravet C, Genton P, Belmonte A, Kaminska A, Dulac O. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia. 1998;39(5):508-512. PubMed PMID: 9596203
  23. Guerrini R, Belmonte A, Genton P. Antiepileptic drug-induced worsening of seizures in children. Epilepsia. 1998;39 Suppl 3:S2-S10. PubMed PMID: 9593229
  24. Laux L, Sullivan J, Perry MS, Brunklaus A, Desurkar A, Schreiber JM, et al. Zorevunersen in Children and Adolescents with Dravet Syndrome. N Engl J Med. 2026;394(10):969-982. PubMed PMID: 41780062

PubMed Topic Searches

  1. PubMed: Dravet syndrome and SCN1A
  2. PubMed: Dravet syndrome, SUDEP and mortality
  3. PubMed: Dravet syndrome randomised trials
  4. PubMed: Dravet syndrome and vaccination
  5. PubMed: sodium-channel blockers and seizure worsening in Dravet syndrome
  6. PubMed: antisense oligonucleotides for Dravet syndrome

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