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Epilepsy: Benign Familial Neonatal Seizures Type 2 via the KCNQ3 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
4305 KCNQ3 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4305KCNQ381479 81479(x2) $640 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.

Turnaround Time

18 days on average for standard orders or 13 days 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

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. Seizures are generally brief, lasting one to two minutes. Seizure types include tonic or apneic episodes, focal clonic activity or autonomic changes. In classic BFNS cases, psychomotor development is not affected. BFNS has a similar clinical presentation to benign familial neonatal-infantile seizures (BFNIS) and benign familial infantile seizures (BFIS) and is largely distinguished from these disorders by an earlier age of onset (Zara et al. 2013). In general, KCNQ3 pathogenic variants cause typical BFNS, however, they can be also found in patients with more severe phenotypes including intellectual disability (Miceli et al 2015).

Genetics

Benign familial neonatal seizures are inherited in an autosomal dominant manner and can be caused by pathogenic variants in KCNQ3 (Wilmshurst et al 2015; Ottman et al 2010). The reported KCNQ3 pathogenic variants are missense, as well as a large deletion encompassing the KCNQ3 locus (Grinton et al. 2015; Allen et al. 2014). The KCNQ3 protein contains six trans-membrane domains and the pore region. BFNS-associated pathogenic variants in KCNQ3 usually affect the pore region of the protein (Charlier et al 1989). The penetrance of KCNQ3 pathogenic variants can be incomplete, which may be due to unrecognized brief manifestation of neuronal seizures.

KCNQ3 is potassium voltage-gated channel, subfamily Q, member 3. It encodes the alpha subunit of the voltage-gated potassium ion channel (Charlier et al 1989). The gene is highly expressed in neurons of the brain. The KCNQ3 alpha subunits co-assemble with alpha subunits of KCNQ2 to form a heteromeric functional potassium channel that transmits a M-current, a slowly activating, non-inactivating potassium conductance that stabilizes membrane potential and inhibits excessive neuronal activity (Bellini et al. 2014). Slight loss of KCNQ2/3 channel activity leads to a hyperexcitability of certain neurons and thereby causes seizures (Jentsch et al 2000).

Clinical Sensitivity - Sequencing with CNV PG-Select

In a large cohort study of benign familial neonatal seizures, a molecular cause in KCNQ2, KCNQ3 or SCN2A was identified in 91% of cases (Grinton et al. 2015). Compared to KCNQ2, pathogenic variants in KCNQ3 are found to be a rare cause in cases of benign familial neonatal seizures (Allen et al. 2014; Grinton et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the KCNQ3 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Testing of the KCNQ2 and KCNQ3 genes should be considered in infants with unexplained tonic or clonic seizures in the first week of life, regardless of family history (Allen et al. 2014).

Gene

Official Gene Symbol OMIM ID
KCNQ3 602232
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Seizures, Benign Familial Neonatal, 2 AD 121201

Citations

  • Allen NM. et al. 2014. Epilepsia. 55: e99-105. PubMed ID: 25052858
  • Bellini G. et al. 2014. KCNQ3-Related Disorders. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 24851285
  • Charlier C. et al. 1998. Nature Genetics. 18: 53-5. PubMed ID: 9425900
  • Grinton BE. et al. 2015. Epilepsia. 56: 1071-80. PubMed ID: 25982755
  • Jentsch TJ. et al. 2000. Epilepsia. 41: 1068-9. PubMed ID: 10961644
  • Miceli F. et al. 2015. Epilepsia. 56: e15-20. PubMed ID: 25524373
  • Ottman R. et al. 2010. Epilepsia 51:655-70. PubMed ID: 20100225
  • Wilmshurst J.M. et al. 2015. Epilepsia. 56: 1185-97. PubMed ID: 26122601
  • Zara F et al. 2013. Epilepsia 54: 425–436. 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

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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.
Total Price: $
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