Epilepsy: Ohtahara Syndrome Sequencing Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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NGS Sequencing

Test Code Test Copy GenesCPT Code Copy CPT Codes
2639 ARX 81404 Add to Order
CDKL5 81406
KCNQ2 81406
KCNT1 81479
PNKP 81479
SCN2A 81479
SLC25A22 81479
SPTAN1 81479
STXBP1 81406
Full Panel Price* $1690.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
2639 Genes x (9) $1690.00 81404, 81406(x3), 81479(x5) Add to Order
Pricing Comment

We are happy to accommodate requests for single genes or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered on our PGxome Custom Panel.

Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Extrapolating from previously published studies in large cohorts of patients with Ohtahara syndrome, we predict that our Ohtahara syndrome NextGen sequencing panel will identify pathogenic variants in approximately 50% of patients (Saitsu and Matsumoto 2011; Nakamura et al. 2013).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 ARX$690.00 81403 Add to Order
CDKL5$690.00 81405
KCNQ2$690.00 81479
KCNT1$690.00 81479
PNKP$690.00 81479
SCN2A$690.00 81479
SLC25A22$690.00 81479
SPTAN1$690.00 81479
STXBP1$690.00 81479
Full Panel Price* $840.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
600 Genes x (9) $840.00 81403, 81405, 81479(x7) Add to Order
Pricing Comment

# of Genes Ordered

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Over 100

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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Clinical sensitivity for large deletions and duplications leading to Ohtahara syndrome in ARX is difficult to estimate because of rare cases and inconsistent diagnosis. 

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Clinical Features

Ohtahara syndrome is one of the most severe and earliest infantile epileptic encephalopathies. It has onset within the first three months of life and often within the first two weeks. Infants manifest tonic spasms which are independent of the sleep cycle. On electroencephalograms (EEG), Ohtahara patients display a characteristic suppression-burst pattern, which comprises a series of high-amplitude spikes and polyspikes that alternate at a regular rate with periods of electric suppression. This suppression-burst pattern is observed in both wakefulness and sleep. One third of patients will develop other seizure types, such as focal motor seizures, hemiconvulsions and generalized tonic-clonic seizures. The prognosis is poor, and patients frequently die during infancy. The survivors invariably suffer psychomotor impairments. Most of patients (75%) will progress into another epileptic disorder, West syndrome, while some patients (12%) will develop Lennox-Gastaut syndrome (Ohtahara and Yamatogi 2006; Beal et al. 2012; Wilmshurst et al. 2015).


This Ohtahara Syndrome NextGen sequencing panel includes ARX, STXBP1 (Ottman et al. 2010; Wilmshurst et al. 2015), as well as SCN2A, KCNQ2, KCNT1, SLC25A22 CDKL5, PNKP and SPTAN1.

ARX encodes aristaless-related homeobox protein. Inheritance is X-linked recessive for this gene (Ottman et al 2010; Wilmshurst et al 2015; Shoubridge et al 2010). Pathogenic variants include point mutations, as well as large deletions/duplications, and large DNA arrangements.

STXBP1 encodes syntaxin binding protein 1. Inheritance is autosomal dominant (Ottman et al 2010; Wilmshurst et al 2015). STXBP1 pathogenic variants are responsible for ~35% of patients with Ohtahara syndrome (Saitsu and Matsumoto 2011). Pathogenic variants include point mutations, as well as large deletions.

SCN2A encodes an alpha subunit of the voltage-gated sodium channel. Inheritance is autosomal dominant. SCN2A pathogenic missense pathogenic variants are responsible for ~14% of patients with Ohtahara syndrome (Nakamura et al 2013). Pathogenic variants include point mutations, as well as large deletions/duplications, and most of them occur de novo.

KCNQ2 encodes a voltage-gated potassium channel. Inheritance is autosomal dominant (Kato et al 2013). Pathogenic variants include point mutations, as well as large deletions.

KCNT1 encodes a sodium-activated potassium channel, subfamily T, member 1. Inheritance is autosomal dominant. The pathogenic variants reported include point variants (Martin et al 2014; Ohba et al 2015).

SLC25A22 encodes solute carrier family 25, member 22 which is the mitochondrial glutamate carrier. Inheritance is autosomal recessive manner. Pathogenic variants reported so far are point variants (Molinari et al 2009).

Other genes are PNKP encoding polynucleotide kinase 3-prime phosphatase, with autosomal recessive inheritance; CDKL5 encoding cyclin-dependent kinase-like 5, with X-linked dominant inheritance; and SPTAN1 encoding the alpha subunit of nonerythrocytic spectrin 1, with autosomal dominant inheritance.

See individual gene test descriptions for more information.

If you would like to analyze additional genes, please see our
1) Early Infantile Epileptic Encephalopathy, dominant and X-linked NextGen sequencing panel (total 24 genes)  #1321
2) Early Infantile Epileptic Encephalopathy NextGen sequencing panel (total 64 genes) #1961

Testing Strategy

For this Next Generation (NextGen) panel, the full coding regions plus ~10 bp of non-coding DNA flanking each exon are sequenced for each of the genes listed below. Sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads. All pathogenic and undocumented variants are confirmed by Sanger sequencing.

Indications for Test

Candidates for this panel include patients with symptoms suspected for Ohtahara syndrome. This panel was made based on recent ILEA recommendation for the management of infantile seizures and especially aids in a differential diagnosis of similar phenotypes by analyzing multiple genes simultaneously (Wilmshurst et al. 2015).


Official Gene Symbol OMIM ID
ARX 300382
CDKL5 300203
KCNQ2 602235
KCNT1 608167
PNKP 605610
SCN2A 182390
SLC25A22 609302
SPTAN1 182810
STXBP1 602926
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Early Infantile Epilepsies and Autism via the SCN2A Gene
Early Infantile Epileptic Encephalopathy and Benign Familial Neonatal Seizures via the KCNQ2 Gene
Early Infantile Epileptic Encephalopathy and Intellectual Disability via the SPTAN1 Gene
Early Infantile Epileptic Encephalopathy and Rett-like Syndrome via the CDKL5 Gene
Early Infantile Epileptic Encephalopathy via the SLC25A22 Gene
Early Infantile Epileptic Encephalopathy, Recessive Sequencing Panel
Early Infantile Epileptic encephalopathy-4/Ohtahara syndrome via the STXBP1 Gene
Early Infantile Epileptic Encephalopathy:
Dominant and X-linked Sequencing Panel
Epilepsy: Dravet Syndrome Sequencing Panel
Epilepsy: Generalized Epilepsy with Febrile Seizures Plus (GEFS+) Sequencing Panel
Malignant Migrating Partial Seizures of Infancy and Autosomal Dominant Nocturnal Frontal Lobe Epilepsy via the KCNT1 Gene
Microcephaly, Seizures and Developmental Delay via the PNKP Gene
X-Linked Intellectual Disability Sequencing Panel with CNV Detection
X-linked Lissencephaly-2 via the ARX Gene


Genetic Counselors
  • Beal JC. et al. 2012. Pediatric Neurology. 47: 317-23. PubMed ID: 23044011
  • Kato M et al. 2013. Epilepsia. 54: 1282-7. PubMed ID: 23621294
  • Martin HC et al. 2014. Human Molecular Genetics. 23: 3200-11. PubMed ID: 24463883
  • Molinari F et al. 2009. Clinical Genetics. 76: 188-94.
    PubMed ID: 19780765
  • Nakamura K et al. 2013. Neurology. 81: 992-8. PubMed ID: 23935176
  • Ohba C et al. 2015. Epilepsia. 56: e121-e128. PubMed ID: 26140313
  • Ohtahara S, Yamatogi Y. 2006. Epilepsy Research. 70 Suppl 1: S58-67. PubMed ID: 16829045
  • Ottman R. et al. 2010. Epilepsia 51:655-70. PubMed ID: 20100225
  • Saitsu H., Matsumoto N. 2011. Developmental Medicine and Child Neurology. 53: 806-7. PubMed ID: 21631463
  • Shoubridge C et al. 2010. Human Mutation. 31: 889-900. PubMed ID: 20506206
  • Wilmshurst J.M. et al. 2015. Epilepsia. 56: 1185-97. PubMed ID: 26122601
Order Kits

NextGen Sequencing using PG-Select Capture Probes

Test Procedure

We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~20 bases of non-coding DNA flanking each exon.  As required, genomic DNA is extracted from the patient specimen.  For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes.  Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA).  Regions with insufficient coverage by NGS are covered by Sanger sequencing.  All pathogenic, likely pathogenic, or variants of uncertain significance are confirmed by Sanger sequencing.

For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions.  After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).

(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign, Common Variants

Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (  Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.

Analytical Validity

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.   

Analytical Limitations

Interpretation of the test results is limited by the information that is currently available.  Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles.  Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion.   In these cases, the report will contain no information about the second allele.  Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).

We sequence all coding exons for each given transcript, plus ~20 bp of flanking non-coding DNA for each exon.  Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.

In most cases, we are unable to determine the phase of sequence variants.  In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited.  Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood).   Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics.  However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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