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Type IV Voltage-Gated Sodium Channel (Alpha Subunit)-Related Disorders via the SCN4A Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11645 SCN4A 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11645SCN4A81406 81406,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Disorders related to the skeletal muscle type 4 voltage-gated sodium channel alpha subunit gene (SCN4A, OMIM 603967) generally share the common feature of flaccid muscle weakness but differ from one another in key clinical findings.  Hyperkalemic periodic paralyisis (HYPP, OMIM 170500) is characterized by elevated serum potassium during attacks of limb weakness and normal potassium levels between attacks.  Average age of onset is two years old (Miller et al. Neurology 63:1647-1655, 2004).   Symptoms can be provoked with oral intake of potassium and alleviated by calcium intake (Jurkat-Rott and Lehmann-Horn, GeneReviews 2011).  Hypokalemic periodic paralysis, type 2 (HOKKP2, OMIM 613345) is characterized by infrequent but severe attacks which may include paralysis, low serum potassium levels, and onset in childhood to adolescence.  Acute symptoms are treated with administration of potassium and long term management is accomplished with diet (low sodium and carbohydrate/high potassium), oral doses of potassium salts, and in some cases with cholinesterase inhibitors (Sternberg et al. GeneReviews, 2009).  Potassium-aggravated myotonia congenita (OMIM 608390) includes three clinical entities: mild myotonia fluctuans (Ricker et al. Arch Neurol 51:1095-1102, 1994), severe myotonia permanens (Colding-Jorgensen et al. Neurology 67:153-155, 2006), and acetazolamide-responsive myotonia (Ptacek et al. Neurology 42:431-433, 1992, Trudell et al. Neurology 37:488-491, 1987).  Clinical symptoms include painful stiffness and cramping induced by exercise, cold temperature, fever, or potassium-rich diet.  Paramyotonia congenita (PMC, OMIM 168300) is characterized by frequent episodes lasting <24 hours, cold-induced myotonia, persistent weakness, increased serum creatine kinase, and normal serum potassium levels (Miller et al. 2004).  Congenital myasthenic syndrome associated with fatigable weakness and recurrent attacks of respiratory and bulbar paralysis (OMIM 614198) has been described in one patient (Tsujino et al. Proc Nat Acad Sci 100:7377-7382, 2003).  The condition resembled infantile CHAT-associated CMS, and affected muscle groups included ocular, facial, limb, and truncal.  The patient was successfully treated with a cholinesterase inhibitor.  Other SCN4A-related conditions include severe congenital episodic laryngospasms (Lion-Francois et al. Neurology 75: 641-645, 2010) and severe painful generalized myotonia with muscle hypertrophy, which was found in French-Canadians (Dupre et al. et al. Neuromusc Disord 19:330-334, 2009).

Genetics

All disorders related to the SCN4A gene are inherited in an autosomal dominant pattern.  Hypokalemic periodic paralysis type 1 is caused by variants in the CACNA1S gene and myotonia congenita type 1 is caused by variants in the CLCN1 gene.  The SCN4A p.Thr704Met and p.Met1592Val variants are common among HYPP patients.

Clinical Sensitivity - Sequencing with CNV PGxome

Among 56 families with HOKKP2 and 47 with HYPP, five and thirty families, respectively, were found to have SCN4A variants (Miller et al. 2004). Among 56 patients with PMC, 49 were found to have SCN4A variants (Miller et al. 2004). The other SCN4A disorders are too rare to estimate clinical sensitivity.

Testing Strategy

This test provides full coverage of all coding exons of the SCN4A gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Clinical presentations consistent with any of the SCN4A-related disorders.

Gene

Official Gene Symbol OMIM ID
SCN4A 603967
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Colding-Jorgensen et al. Neurology 67:153-155, 2006 PubMed ID: 16832098
  • Dupre et al. et al. Neuromusc Disord 19:330-334, 2009 PubMed ID: 18337100
  • Jurkat-Rott and Lehmann-Horn. (2004). Hyperkalemic Periodic Paralysis Type 1. GeneReviews. PubMed ID: 20301669
  • LionFrancois et al. Neurology 75: 641-645, 2010 PubMed ID: 20713951
  • Miller et al. Neurology 63:1647-1655, 2004 PubMed ID: 15534250
  • Ptacek et al. Neurology 42:431-433, 1992 PubMed ID: 1310531
  • Ricker et al. Arch Neurol 51:1095-1102, 1994 PubMed ID: 7980103
  • Sternberg et al. GeneReviews, 2009 PubMed ID: 20301512
  • Trudell et al. Neurology 37:488-491, 1987 PubMed ID: 3822145
  • Tsujino et al. Proc Nat Acad Sci 100:7377-7382, 2003 PubMed ID: 12766226

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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.
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