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Disease Profile

Dravet syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

G40.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Severe Myoclonic Epilepsy of Infancy; SMEI; Myoclonic epilepsy, severe, of infancy;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Dravet syndrome is the most severe of a group of conditions known as SCN1Arelated seizure disorders. Symptoms include seizures which first occur in infancy that are often triggered by high temperatures (febrile seizures). In childhood, many types of seizures may occur and they may increase in frequency. Seizures may be difficult to treat. Other symptoms include loss of motor skills, intellectual disability, speech impairment, and difficulty with movement. Most cases of Dravet syndrome occur when the SCN1A gene is not working correctly. It can be inherited in an autosomal dominant pattern, but most people with Dravet syndrome do not have a family history of the condition. Diagnosis is based on a clinical exam, medical history, and the results of genetic testing. The main goal of treatment is to reduce the number and length of seizures.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with Dravet syndrome. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms include: 

  • Many different types of seizures
  • Sudden muscle jerking (myoclonus)
  • Loss of developmental skills
  • Intellectual disability
  • Problems with walking
  • Speech impairment
  • Autistic-like behavior

The first seizures appear before one year of age and are often associated with fevers. In childhood, other types of seizures develop, and the frequency of seizures increases. Loss of developmental and cognitive skills may occur along with speech impairment and difficulty walking. In adulthood, the number of seizures may decrease, and nighttime seizures may occur. More serious complications include the risk of continuous seizures (status epilepticus) and sudden unexplained death.[1][2][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Progressive gait ataxia
0007240
30%-79% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Atypical absence seizure
0007270
Autistic behavior
0000729
Bradykinesia
Slow movements
Slowness of movements

[ more ]

0002067
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Cogwheel rigidity
0002396
Complex febrile seizure
0011172
Epilepsia partialis continua
0012847
Facial tics
Cramping of facial muscles
Facial spasms
Jerking of facial muscles
Mimic spasms
Spasms of facial muscles
Twitching of facial muscles

[ more ]

0011468
Focal aware seizure
0002349
Focal hemiclonic seizure
0006813
Focal impaired awareness seizure
0002384
Generalized clonic seizure
0011169
Limited neck range of motion
0000466
Multifocal epileptiform discharges
0010841
Myoclonus
0001336
Obsessive-compulsive trait
Obsessive-compulsive traits
0008770
Parkinsonism
0001300
Photosensitive myoclonic seizure
0001327
Photosensitive tonic-clonic seizure
0007207
5%-29% of people have these symptoms
Action tremor
0002345
Cyanotic episode
0200048
Drooling
Dribbling
0002307
Dysgenesis of the hippocampus
0025101
EEG with generalized epileptiform discharges
0011198
Global brain atrophy
Generalized brain degeneration
0002283
Impulsivity
Impulsive
0100710
Incoordination
Difficulties in coordination
Incoordination of limb movements
Limb incoordination

[ more ]

0002311
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Limited knee extension
0003066
Pallor
0000980
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Pes valgus
0008081
Poor fine motor coordination
0007010
Short attention span
Poor attention span
Problem paying attention

[ more ]

0000736
Status epilepticus without prominent motor symptoms
0031475
Tibial torsion
0100694
1%-4% of people have these symptoms
Generalized tonic seizure
0010818
Percent of people who have these symptoms is not available through HPO
Abnormal pyramidal sign
0007256
Ataxia
0001251
Atonic seizure
0010819
Autosomal dominant inheritance
0000006
Cerebral atrophy
Degeneration of cerebrum
0002059
Cerebral visual impairment
0100704
Epileptic encephalopathy
0200134
Generalized myoclonic seizure
0002123
Generalized non-motor (absence) seizure
Brief seizures with staring spells
0002121
Global developmental delay
0001263
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Motor delay
0001270
Myoclonic seizure
0032794
Postnatal microcephaly
0005484
Status epilepticus
Repeated seizures without recovery between them
0002133
Visually-induced seizure
0020216

Cause

Dravet syndrome occurs when the SCN1A gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[2] 

DNA changes in the SCN1B, GABRG2, SCN2A and several other genes are associated with seizure disorders with similar symptoms to Dravet syndrome.[3]

Diagnosis

Dravet syndrome is diagnosed based on the results of a clinical exam looking for specific symptoms that have been previously seen in this condition.[5] Genetic testing can also be helpful.[2]

Diagnosis is important because certain antiseizure medications (sodium-channel agents) can make the seizures worse in Dravet syndrome.[2]

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment

Treatment for Dravet syndrome is focused on reducing the number and length of seizures. The seizures seen with Dravet syndrome are usually difficult to control, and people with this condition often need to take multiple anti-seizure medications. Certain types of anti-seizure medications (sodium-channel agents) can make the seizures worse and should be avoided. New medications are being tested that are proven to be helpful in this condition.[2][3] 

Specialists who may be involved in the care of someone with Dravet syndrome include:

  • Neurologist
  • Developmental pediatrician
  • Physical therapist
  • Occupational therapist
  • Speech therapist

Management Guidelines

  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • Stiripentol(Brand name: Diacomit) Manufactured by Biocodex
      FDA-approved indication: August 2018, stiripentol (Diacomit) was approved for the treatment of seizures associated with Dravet syndrome (DS) in patients 2 years of age and older taking clobazam.
      National Library of Medicine Drug Information Portal
    • Cannabidiol(Brand name: Epidiolex) Manufactured by GW Pharma Ltd.
      FDA-approved indication: June 2018, cannabidiol (Epidiolex) was approved for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older. Sept 2018, the DEA (US Drug Enforcement Agency) placed Epidolex in schedule V of Controlled Substance Act. However, availability may be dependent on laws of individual States.
      National Library of Medicine Drug Information Portal
      Medline Plus Health Information
    • Fenfluramine HCI(Brand name: Fintepla) Manufactured by Zogenix, Inc
      FDA-approved indication: Fintepla (fenfluramine) is indicated for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older.
      National Library of Medicine Drug Information Portal

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

      • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

        Organizations Providing General Support

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Dravet syndrome. Click on the link to view a sample search on this topic.

              References

              1. Lagae L, Brambilla I, Mingorance A, Gibson E, Battersby A. Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey. Dev Med Child Neurol. 2018; 60(1):63-72. https://pubmed.ncbi.nlm.nih.gov/28984349.
              2. Gataullina S, Dlac O. From genotype to phenotype in Dravet disease. Seizure. 2017; 44:58-64. https://pubmed.ncbi.nlm.nih.gov/27817982.
              3. Knupp KG, Wirrell EC. Treatment Strategies for Dravet Syndrome [published correction appears in CNS Drugs. 2018 Aug;32(8):783. Abstract corrected].. CNS Drugs. 2018; 32(4):335-350. https://pubmed.ncbi.nlm.nih.gov/29594870.
              4. Miller IO & Sotero de Menezes MA. SCN1A-Related Seizure Disorders. GeneReviews. May, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1318/.
              5. Wirrell EC, Laux L, Donner E, et al.. Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel.. Pediatr Neurol. 2017;68:18-34.e3.. 2017; 68:18-34.e.3. https://pubmed.ncbi.nlm.nih.gov/28284397.
              6. Wu YW, Sullivan J, McDaniel SS, et al. Incidence of Dravet Syndrome in a US Population. Pediatrics. 2015; 136(5):e1310-1315. https://pubmed.ncbi.nlm.nih.gov/26438699.
              7. Epileptic encephalopathy, early infantile, 6 (EIEE6). Online Mendelian Inheritance in Man (OMIM). Updated 7/9/2016; https://omim.org/entry/607208.
              8. Dravet syndrome. Orphanet. 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33069.

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