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Dravet Syndrome and Generalized Epilepsy with Febrile Seizures Plus via the SCN1A Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
3043 SCN1A 81407 81407,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3043SCN1A81407 81407,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Dravet syndrome (DS; OMIM: 607208) is one of a group of early infantile epileptic encephalopathies (EIEE). DS is characterized by the onset of seizures within the first year of life in children with previously normal psychomotor development. Early seizures can be clonic or clonic-tonic and are usually brought on by fever. Early EEGs of DS patients reveal no electroclinical abnormalities, but a generalized spike wave pattern is seen as the disease progresses. DS is characterized by the presence of multiple seizure types within patients, including: myoclonic jerks, absence seizures, focal seizures, photosensitive seizures and prolonged seizures resulting in status epilepticus (Akiyama et al. 2012). Seizures observed in DS are resistant to treatment with anti-epileptic drugs. DS patients suffer severe cognitive and motor impairments that persist throughout their lives.

Genetics

Dravet syndrome is an autosomal dominant condition caused by loss of function mutations in SCN1A, which can include missense, nonsense and splice site mutations as well as insertions or deletions that disrupt the reading frame. The majority (94%) of mutations in SCN1A associated with DS arise de novo (Vadlamudi et al. 2010). Thus, DS cases are sporadic, occurring in individuals with no family history of Dravet syndrome. Rare cases of inherited DS are seen in situations where the proband's parent was mosaic for the causative SCN1A variant.

Mutations in SCN1A can also cause Generalized epilepsy with febrile seizures plus (GEFS+, OMIM:604403). GEFS+ is a milder infantile seizure disorder characterized by febrile seizures. GEFS+ is associated with missense mutations in SCN1A (Guerrini et al. 2010). GEFS+ cases can be sporadic or inherited in an autosomal dominant manner.

SCN1A encodes a neuronally expressed alpha subunit of the voltage-gated sodium channel. Sodium channels are excitatory and propagate action potentials in neurons. Epilepsy disorders are characterized by hyperexcitability of neurons. SCN1A-containing sodium channels normally activate a set of inhibitory neurons in the neocortex and hypothalamus. These inhibitory neurons release a neurotransmitter, GABA, which is important for balancing excitation and inhibition in the brain. It is proposed that mutations in SCN1A relieve GABAergic inhibition in the neocortex and hypothalamus, resulting in neuronal hyperactivity and epilepsy (Yu et al. 2006; Catterall et al. 2010).

Clinical Sensitivity - Sequencing with CNV PG-Select

Causative variants in SCN1A have been reported in 79% (52 of 66) of patients with Dravet syndrome (Harkin et al. 2007). Causative SCN1A variants are detected in ~10% of patients with GEFS+ (Scheffer et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the SCN1A gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for SCN1A testing include patients who display clinical features of Dravet syndrome. Normal development prior to seizure onset and seizures that are sensitive to elevated body temperature are two symptoms which are strong indicators for SCN1A testing (Fountain-Capal et al. 2011).

Gene

Official Gene Symbol OMIM ID
SCN1A 182389
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Generalized Epilepsy with Febrile Seizures Plus and Dravet syndrome via the SCN1B Gene

Citations

  • Akiyama M. et al. 2012. Acta Medica Okayama. 66: 369-76. PubMed ID: 23093055
  • Catterall WA et al. 2010. The Journal of Physiology. 588: 1849-59. PubMed ID: 20194124
  • Fountain-Capal JK, Holland KD, Gilbert DL, Hallinan BE. 2011. When Should Clinicians Order Genetic Testing for Dravet Syndrome? Pediatric Neurology 45: 319323. PubMed ID: 22000312
  • Guerrini R et al. 2010. Epilepsia. 51: 2474-7. PubMed ID: 21204810
  • Harkin LA. et al. 2007. Brain : a Journal of Neurology. 130: 843-52. PubMed ID: 17347258
  • Scheffer IE. et al. 2009. Brain and Development 31: 394400. PubMed ID: 19203856
  • Vadlamudi L. et al. 2010. The New England Journal of Medicine. 363: 1335-40. PubMed ID: 20879882
  • Yu FH et al. 2006. Nature Neuroscience. 9: 1142-9. PubMed ID: 16921370

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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