DNA icon

Early Infantile Epilepsies and Autism via the SCN2A 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
4227 SCN2A 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4227SCN2A81479 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-infantile seizures (BFNIS; OMIM:607745) is an infantile onset epilepsy disorder. Sudden onset of seizures occurs between 2 days to 13 months, with median onset being 2-3 months (Herlenius et al. 2007). BFNIS presents as clusters of afebrile seizures with 2-20 per day. Seizures are brief, lasting 10-180 seconds and begin with eye rolling or blinking and then progress to tonic or clonic movements (Herlenius et al. 2007). EEG recording reveals that seizures have a focal onset and then secondarily generalize. Rarely do BFNIS patients experience seizures outside of the infantile period. Intellectual ability or motor skills are not impaired in BFNIS patients.

Early infantile epileptic encephalopathy (EIEE; OMIM:613721) encompasses a range of infantile onset seizure disorders which often impair cognitive and motor development. Mutations in SCN2A have been implicated in both Dravet and Ohtahara syndromes, two EIEEs with well characterized clinical phenotypes. Dravet syndrome (DS) presents as seizures within the first year of life in children with previously normal psychomotor development. DS is characterized by the presence of multiple seizure types within a patient. Early seizures are usually brought on by fever (Akiyama et al. 2012). DS patients suffer severe cognitive and motor impairments that persist throughout their lives. Ohtahara syndrome (OS) presents as tonic spasms within the first three months of life. These seizures are often resistant to treatment with anticonvulsants. OS patients display a characteristic suppression-burst pattern on EEG recordings (Saitsu et al. 2008). OS is highly progressive, resulting in severe cognitive and motor impairments (Ohtahara and Yamatogi 2006).

Autism is a communication disorder that often co-occurs with intellectual disability and epilepsy, suggesting a shared etiology. Several genome-wide sequencing studies of patients with an Autism Spectrum Disorder have revealed de novo nonsense and splice site mutations in the SCN2A gene (Jiang et al. 2013; Rauch et al. 2012; Sanders et al. 2012).

Genetics

BFNIS is inherited in an autosomal dominant manner and is caused by missense mutations in the SCN2A gene (Berkovic et al. 2004). Ohtahara syndrome, Dravet syndrome and other SCN2A-related epileptic encephalopathies can be inherited in an autosomal dominant manner but more often occur as sporadic cases resulting from de novo mutations in the SCN2A gene (Ogiwara et al. 2009; Nakamura et al. 2013).

SCN2A 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 and improper neuronal firing. Missense mutations in SCN2A found in BFNIS have been shown to mildly impair sodium channel function whereas missense mutations seen in epileptic encephalopathy cases more strongly impair channel function (Shi et al. 2012). This suggests that loss of SCN2A activity underlies the epilepsy phenotype.

Clinical Sensitivity - Sequencing with CNV PG-Select

Inherited SCN2A mutations were found in 6 of 11 families (~54%) diagnosed with BFNIS (Berkovic et al. 2004). Pathogenic de novo variants in SCN2A were identified in 13.4% (9 of 67) of patients with Ohathara syndrome and in whom no variants in STXBP1 and KCNQ2 were identified (Nakamura et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the SCN2A gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

SCN2A testing should be considered for patients with symptoms of BFNIS and family history consistent with autosomal dominant inheritance. SCN2A sequencing should also be considered in cases of early infantile epileptic encephalopathy, particularly in STXBP1 or KCNQ2 -negative cases of Ohtahara syndrome or SCN1A -negative cases of Dravet syndrome (Nakamura et al. 2013).

Gene

Official Gene Symbol OMIM ID
SCN2A 182390
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Akiyama M. et al. 2012. Acta Medica Okayama. 66: 369-76. PubMed ID: 23093055
  • Berkovic SF, Heron SE, Giordano L, Marini C, Guerrini R, Kaplan RE, Gambardella A, Steinlein OK, Grinton BE, Dean JT, Bordo L, Hodgson BL, et al. 2004. Benign familial neonatal-infantile seizures: Characterization of a new sodium channelopathy. Annals of Neurology 55: 550–557. PubMed ID: 15048894
  • Herlenius E, Heron SE, Grinton BE, Keay D, Scheffer IE, Mulley JC, Berkovic SF. 2007. SCN2A Mutations and Benign Familial Neonatal-Infantile Seizures: The Phenotypic Spectrum. Epilepsia 48: 1138–1142. PubMed ID: 17386050
  • Jiang Y, Yuen RKC, Jin X, Wang M, Chen N, Wu X, Ju J, Mei J, Shi Y, He M, Wang G, Liang J, et al. 2013. Detection of Clinically Relevant Genetic Variants in Autism Spectrum Disorder by Whole-Genome Sequencing. The American Journal of Human Genetics 93: 249–263. PubMed ID: 23849776
  • Nakamura K et al. 2013. Neurology. 81: 992-8. PubMed ID: 23935176
  • Ogiwara I, Ito K, Sawaishi Y, Osaka H, Mazaki E, Inoue I, Montal M, Hashikawa T, Shike T, Fujiwara T, Inoue Y, Kaneda M, et al. 2009. De novo mutations of voltage-gated sodium channel II gene SCN2A in intractable epilepsies. Neurology 73: 1046–1053. PubMed ID: 19786696
  • Ohtahara S, Yamatogi Y. 2006. Epilepsy Research. 70 Suppl 1: S58-67. PubMed ID: 16829045
  • Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Donato N Di. 2012. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. The Lancet. PubMed ID: 23020937
  • Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, Tohyama J, Uruno K, Kumada S, Nishiyama K, Nishimura A, Okada I, Yoshimura Y, Hirai S, Kumada T, Hayasaka K, Fukuda A, Ogata K, Matsumoto N. 2008. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet 40:782-788. PubMed ID: 18469812
  • Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, et al. 2012. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485: 237–241. PubMed ID: 22495306
  • Shi X, Yasumoto S, Kurahashi H, Nakagawa E, Fukasawa T, Uchiya S, Hirose S. 2012. Clinical spectrum of SCN2A mutations. Brain and Development 34: 541–545. PubMed ID: 22029951

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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×