Early Infantile Epileptic Encephalopathy via the SCN8A Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4229 | SCN8A | 81479 | 81479,81479 | $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
Early infantile epileptic encephalopathy 13 (EIEE13; OMIM:614558) is characterized by the onset of refractory epilepsy during the first 6 months of life. Other features of EIEE13 include intellectual disability, regression of language skills, developmental delay and repetitive behaviors (Veeramah et al. 2012).
Genetics
EIEE13 is inherited in an autosomal dominant manner and is caused by heterozygous mutations in the SCN8A gene. A number of de novo missense mutations in SCN8A have been identified in whole exome sequencing studies of patients with severe epilepsy of unknown cause (Allen et al. 2013; Carvill et al. 2013). SCN8A encodes a neuronally expressed subunit of the voltage-gated sodium channel. A heterozygous missense mutation of SCN8A in a mouse model results in spike-wave discharges on EEGs and increased seizure susceptibility (Papale et al. 2009).
Clinical Sensitivity - Sequencing with CNV PG-Select
In a recent study of patients with early onset epileptic encephalopathy, de novo SCN8A variants were identified in 7 of 261 (~2.7%) patients (Ohba et al. 2014). Previously, SCN8A was sequenced in 500 patients with varying epilepsy diagnoses and was found at a frequency ~0.6% (3 of 500) (Carvill et al. 2013).
Testing Strategy
This test provides full coverage of all coding exons of the SCN8A gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for SCN8A sequencing include patients with onset of intractable seizures during infancy.
Candidates for SCN8A sequencing include patients with onset of intractable seizures during infancy.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SCN8A | 600702 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Epileptic Encephalopathy, Early Infantile, 13 | AD | 614558 |
Citations
- Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR. 2013. De novo mutations in epileptic encephalopathies. Nature 501: 217–221. PubMed ID: 23934111
- Carvill GL, Heavin SB, Yendle SC, McMahon JM, O’Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC. 2013. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nature Genetics 45: 825–830. PubMed ID: 23708187
- Ohba C, Kato M, Takahashi S, Lerman-Sagie T, Lev D, Terashima H, Kubota M, Kawawaki H, Matsufuji M, Kojima Y, Tateno A, Goldberg-Stern H, et al. 2014. Early onset epileptic encephalopathy caused by de novo SCN8A mutations. Epilepsia n/a–n/a. PubMed ID: 24888894
- Papale LA, Beyer B, Jones JM, Sharkey LM, Tufik S, Epstein M, Letts VA, Meisler MH, Frankel WN, Escayg A. 2009. Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice. Human Molecular Genetics 18: 1633–1641. PubMed ID: 19254928
- Veeramah KR, O’Brien JE, Meisler MH, Cheng X, Dib-Hajj SD, Waxman SG, Talwar D, Girirajan S, Eichler EE, Restifo LL, Erickson RP, Hammer MF. 2012. De Novo Pathogenic SCN8A Mutation Identified by Whole-Genome Sequencing of a Family Quartet Affected by Infantile Epileptic Encephalopathy and SUDEP. The American Journal of Human Genetics 90: 502–510. PubMed ID: 22365152
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
Specimen Requirements and Shipping Details
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