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Early Infantile Epileptic Encephalopathy and Benign Familial Neonatal Seizures via the KCNQ2 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
4695 KCNQ2 81406 81406,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4695KCNQ281406 81406,81479 $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

Early infantile epileptic encephalopathy-7 (EIEE7) is a seizure disorder characterized by infantile onset of clonic-tonic seizures and moderate to profound intellectual disability. Symptoms of EIEE7 include: hypotonia, onset of refractory seizures during infancy, burst suppression EEG readings that evolve into to multifocal eplileptiform activity and delayed psychomotor development (Kato et al. 2013). Symptoms of EIEE7 largely overlap with those of Ohtahara Syndrome (OMIM: 308350). Benign familial neonatal seizures (BFNS) are clusters of seizures that occur within the first week of life. Normal development is seen prior to seizure onset and seizures spontaneously remit by 12 months of age (Zara et al. 2013). In classic BFNS cases, psychomotor development is not affected, but some BFNS cases evolve into more severe seizure disorders such as EIEE7. BFNS has a similar clinical presentation to benign familial neonatal-infantile seizures (BFNIS; OMIM:121201) and benign familial infantile seizures (BFIS; OMIM:605751) and is largely distinguished from these disorders by an earlier age of onset (Zara et al. 2013).

Genetics

EIEE7 is caused by heterozygous missense mutations in the KCNQ2 gene. Most cases of EIEE7 are sporadic, resulting from de novo mutations in KCNQ2. BFNS is inherited in an autosomal dominant manner and can be caused by missense and nonsense mutations in KCNQ2 as well as deletions or duplications of the KCNQ2 locus (Heron et al. 2007). KCNQ2 encodes a subunit of the neuronally expressed voltage-gated potassium (K+) ion channel. These K+ channels are responsible for dampening membrane sensitivity of surrounding channels. Loss of K+ channels is believed to result in neuronal hyperexcitability. BFNS is associated with deletions or loss of function mutations in KCNQ2, suggesting that KCNQ2 haploinsufficiency underlies the BFNS phenotype. In contrast, EIEE7 is caused largely by missense mutations in KCNQ2, it is believed that these mutations act in a dominant-negative fashion. Potassium channels are tetramers, requiring the assembly of four functional subunits. Studies in mice have shown that missense mutations in critical domains of KCNQ2 can assemble with wild-type subunits and impede their function, resulting in a more severe phenotype than simple haploinsufficiency of KCNQ2 (Peters et al. 2004).

Clinical Sensitivity - Sequencing with CNV PG-Select

KCNQ2 mutations have been reported in ~20% of Ohtahara-like EIEE cases in which mutations in STXBP1 or ARX (in males) were previously excluded (Milh et al. 2013; Kato et al. 2013). KCNQ2 deletions and single nucleotide variants were reported in 88% (7 of 8) of families diagnosed with BFNS and 67% (6 of 9) of families diagnosed with BFNIS (Zara et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the KCNQ2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

KCNQ2 sequencing is recommended in cases of EIEE/Ohtahara syndrome in which mutations in STXBP1 or ARX (in males) have not been identified (Kato et al. 2013). Candidates for KCNQ2 testing also include patients with symptoms of BFNS who have at least 2 first-degree relatives that were affected by focal seizures within the first 4 months of life (Zara et al. 2013).

Gene

Official Gene Symbol OMIM ID
KCNQ2 602235
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Heron SE, Cox K, Grinton BE, Zuberi SM, Kivity S, Afawi Z, Straussberg R, Berkovic SF, Scheffer IE, Mulley JC. 2007. Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures. Journal of Medical Genetics 44: 791796. PubMed ID: 17675531
  • Kato M et al. 2013. Epilepsia. 54: 1282-7. PubMed ID: 23621294
  • Milh M, Boutry-Kryza N, Sutera-Sardo J, Mignot C, Auvin S, Lacoste C, Villeneuve N, Roubertie A, Heron B, Carneiro M. 2013. Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2. Orphanet journal of rare diseases 8: 80. PubMed ID: 23692823
  • Peters HC, Hu H, Pongs O, Storm JF, Isbrandt D. 2004. Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. Nature Neuroscience 8: 5160. PubMed ID: 15608631
  • Zara F et al. 2013. Epilepsia 54: 425436. PubMed ID: 23360469

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

1) Select Test Method (Platform)


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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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