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 ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
3043 | SCN1A | 81407 | 81407,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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.
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).
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 |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
Generalized Epilepsy With Febrile Seizures Plus, Type 2 | AD | 604403 |
Severe Myoclonic Epilepsy In Infancy | AD | 607208 |
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: 319–323. 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: 394–400. 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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.