Early Infantile Epileptic Encephalopathy, Recessive Sequencing Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits

NGS Sequencing

Test Code Test Copy GenesCPT Code Copy CPT Codes
1905 ACY1 81479 Add to Order
ADSL 81479
ALDH7A1 81406
ARFGEF2 81479
BCKDK 81479
CLN3 81479
CLN5 81479
CLN6 81479
CLN8 81479
CNTNAP2 81406
CSTB 81404
CTSD 81479
CTSF 81479
EPM2A 81404
FARS2 81479
FOLR1 81479
GAMT 81479
GOSR2 81479
KCNJ10 81404
KCTD7 81479
MFSD8 81479
NHLRC1 81403
NRXN1 81479
PIGO 81479
PLCB1 81479
PNKP 81479
PNPO 81479
POLG 81406
PPT1 81479
ROGDI 81479
SCARB2 81479
SLC19A3 81479
SLC25A22 81479
ST3GAL3 81479
ST3GAL5 81479
SZT2 81479
TBC1D24 81479
TNK2 81479
TPP1 81479
WWOX 81479
Full Panel Price* $1290.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
1905 Genes x (40) $1290.00 81403, 81404(x3), 81406(x3), 81479(x33) 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 of next generation sequencing in large cohorts of patients with EIEE, we predict that our Recessive EIEE Panel will identify pathogenic variants in 0.4-12% of patients with EIEE of unknown cause (Lemke et al. 2012; Carvill et al. 2013; Mina et al. 2014).

See More

See Less

Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 ACY1$690.00 81479 Add to Order
ADSL$690.00 81479
ALDH7A1$690.00 81479
ARFGEF2$690.00 81479
BCKDK$690.00 81479
CLN3$690.00 81479
CLN5$690.00 81479
CLN6$690.00 81479
CLN8$690.00 81479
CNTNAP2$690.00 81479
CSTB$690.00 81479
CTSD$690.00 81479
CTSF$690.00 81479
EPM2A$690.00 81479
FARS2$690.00 81479
FOLR1$690.00 81479
GAMT$690.00 81479
GOSR2$690.00 81479
KCNJ10$690.00 81479
KCTD7$690.00 81479
MFSD8$690.00 81479
NHLRC1$690.00 81479
NRXN1$690.00 81479
PLCB1$690.00 81479
PNKP$690.00 81479
PNPO$690.00 81479
POLG$690.00 81479
PPT1$690.00 81479
ROGDI$690.00 81479
SCARB2$690.00 81479
SLC19A3$690.00 81479
SLC25A22$690.00 81479
ST3GAL3$690.00 81479
ST3GAL5$690.00 81479
SZT2$690.00 81479
TBC1D24$690.00 81479
TNK2$690.00 81479
TPP1$690.00 81479
Full Panel Price* $1670.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
600 Genes x (38) $1670.00 81479(x38) Add to Order
Pricing Comment

# of Genes Ordered

Total Price













Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Pathogenic gross deletions have been reported for the CNTNAP2 and NRXN1 genes (Human Gene Mutation Database). In a study of copy number variants in 315 patients with epileptic encephalopathies, one patient was identified with a homozygous CNTNAP2 deletion (Mefford et al. 2011).

See More

See Less

Clinical Features

Early Infantile Epileptic Encephalopathy (EIEE) is a clinically and genetically heterogeneous neurodevelopmental disorder. The key feature of EIEE is onset of frequent and/or severe seizures within the first few weeks of life (Noh et al. 2012). These seizures are often associated with febrile events and may be refractory to treatment with anti-epileptic drugs (AEDs). EIEE patients may also present with an abnormal EEG pattern. Intellectual disability and psychomotor delay are common features of many severe epileptic encephalopathies.


The most common causes of EIEE in infants are structural brain abnormalities and inborn errors of metabolism (Sharma and Prasad 2013). However, in cases of EIEE in which structural or metabolic defects are lacking, genetic factors are being found to play an increasing role. EIEE is a genetically heterogeneous disorder, and over 100 genes have been suggested to be involved in disease pathogenesis (Lemke et al. 2012). EIEE can be inherited in an autosomal recessive manner. This panel involves the sequencing of 40 genes in which homozygous or compound heterozygous variants have been reported to cause EIEE. This panel tests for several well-characterized conditions in which seizures are a predominant feature such as: neuronal ceroid lipofuscinosis, Lafora disease (EPM2A, NHLRC1), metabolic disorders (FOLR1, GAMT, ALDH7A1, PNPO, SLC19A3) and mitochondrial disease (POLG, FARS2, SLC25A22). See individual gene test descriptions for information on molecular biology of gene products.

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

Testing is recommended for patients with severe infantile onset seizures for which a recessive mode of inheritance is suspected.


Name Inheritance OMIM ID
Adenylosuccinate Lyase Deficiency 103050
Aminoacylase 1 Deficiency 609924
Amish Infantile Epilepsy Syndrome 609056
Basal Ganglia Disease, Biotin-Responsive 607483
Branched-chain ketoacid dehydrogenase kinase deficiency 614923
Cerebral Folate Deficiency 613068
Ceroid Lipofuscinosis Neuronal 1 256730
Ceroid Lipofuscinosis Neuronal 10 610127
Ceroid Lipofuscinosis Neuronal 13 615362
Ceroid Lipofuscinosis Neuronal 2 204500
Ceroid Lipofuscinosis Neuronal 3 204200
Ceroid Lipofuscinosis Neuronal 4A, Autosomal Recessive 204300
Ceroid Lipofuscinosis Neuronal 5 256731
Ceroid Lipofuscinosis Neuronal 6 601780
Ceroid Lipofuscinosis Neuronal 7 610951
Ceroid Lipofuscinosis Neuronal 8 600143
Ceroid Lipofuscinosis Neuronal 8, Northern Epilepsy Variant 610003
Combined oxidative phosphorylation deficiency 14 614946
Cortical Dysplasia-Focal Epilepsy Syndrome 610042
Deficiency Of Guanidinoacetate Methyltransferase 612736
DOOR syndrome 220500
Epilepsy, Progressive Myoclonic 3 611726
Epilepsy, Progressive Myoclonic 4, With Or Without Renal Failure 254900
Epilepsy, Progressive Myoclonic 6 614018
Epileptic Encephalopathy, Early Infantile, 10 613402
Epileptic Encephalopathy, Early Infantile, 12 613722
Epileptic Encephalopathy, Early Infantile, 15 615006
Epileptic Encephalopathy, Early Infantile, 16 615338
Epileptic encephalopathy, early infantile, 18 615476
Epileptic Encephalopathy, Early Infantile, 3 609304
Heterotopia, Periventricular, Autosomal Recessive 608097
Hyperphosphatasia with mental retardation syndrome 2 614749
Kohlschutter-Tonz syndrome 226750
Lafora Disease 254780
Myoclonic Epilepsy, Familial Infantile 605021
Pitt-Hopkins-like syndrome 2 614325
Progressive Sclerosing Poliodystrophy 203700
Pyridoxal 5'-Phosphate-Dependent Epilepsy 610090
Pyridoxine-Dependent Epilepsy 266100
SeSAME Syndrome 612780
Spinocerebellar ataxia, autosomal recessive 12 614322
Unverricht-Lundborg Syndrome 254800

Related Tests

POLG-Related Mitochondrial Disorders via the POLG Gene
Adenylosuccinase Deficiency via the ADSL Gene
Amelogenesis Imperfecta Sequencing Panel with CNV Detection
Aminoacylase-1 Deficiency via the ACY1 Gene
Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Sequencing Panel with CNV Detection
Autosomal Recessive Retinitis Pigmentosa Sequencing Panel with CNV Detection
Autosomal-Recessive Intellectual Disability via the NRXN1 Gene
Biotin-Thiamine-Responsive Basal Ganglia Disease via the SLC19A3 Gene
Branched-Chain Ketoacid Dehydrogenase Kinase Deficiency via the BCKDK Gene
Cerebral Folate Deficiency via the FOLR1 Gene
Combined Oxidative Phosphorylation Deficiency 14 via the FARS2 Gene
Cortical Dysplasia-Focal Epilepsy Syndrome via the CNTNAP2 Gene
Creatine Deficiency Syndrome via the GAMT Gene
Disorders of Folate Metabolism and Transport Sequencing Panel
Disorders of Sex Development and Infertility Sequencing Panel with CNV Detection
Disorders of Sex Development Sequencing Panel with CNV Detection
DOORS Syndrome and TBC1D24-related Epilepsy via the TBC1D24 Gene
Dystroglycan-Related Congenital Muscular Dystrophy Sequencing Panel
Early Infantile Epileptic Encephalopathy via the SLC25A22 Gene
Early Infantile Epileptic Encephalopathy via the SZT2 Gene
Early Infantile Epileptic Encephalopathy-12 via the PLCB1 Gene
Early Infantile Epileptic Encephalopathy-15 and Intellectual Disability via the ST3GAL3 Gene
Epilepsy: Ohtahara Syndrome Sequencing Panel
Female Infertility Sequencing Panel with CNV Detection
GM3 Synthase Deficiency via The ST3GAL5 Gene
Hyperphosphatasia with Intellectual Disability via the PIGO Gene
Hypomagnesemia Sequencing Panel with CNV Detection
Kohlschutter-Tonz syndrome (KTS) via the ROGDI Gene
Lafora Disease via the EPM2A Gene
Lafora Disease via the NHLRC1 Gene
Male Infertility Sequencing Panel with CNV Detection
Metabolic Myopathies, Rhabdomyolysis and Exercise Intolerance Sequencing Panel
Microcephaly, Seizures and Developmental Delay via the PNKP Gene
Mitochondrial Complex I Deficiency Sequencing Panel with CNV Detection (Nuclear Genes)
Mitochondrial Genome Maintenance/Integrity Nuclear Genes Sequencing Panel
Nephrotic Syndrome (NS)/Focal Segmental Glomerulosclerosis (FSGS) Sequencing Panel
Neuronal Ceroid Lipofuscinoses (Batten Disease) Sequencing Panel
Neuronal Ceroid Lipofuscinosis 1 via the PPT1 Gene
Neuronal Ceroid Lipofuscinosis 10 via the CTSD Gene
Neuronal Ceroid Lipofuscinosis 13 via the CTSF Gene
Neuronal Ceroid Lipofuscinosis 14 via the KCTD7 Gene
Neuronal Ceroid Lipofuscinosis 2 via the TPP1 Gene
Neuronal Ceroid Lipofuscinosis 3 (Batten Disease) via the CLN3 c.461-280_677+382 Deletion
Neuronal Ceroid Lipofuscinosis 3 via the CLN3 Gene
Neuronal Ceroid Lipofuscinosis 5 via the CLN5 Gene
Neuronal Ceroid Lipofuscinosis 6 via the CLN6 Gene
Neuronal Ceroid Lipofuscinosis 7 via the MFSD8 Gene
Neuronal Ceroid Lipofuscinosis 8 via the CLN8 Gene
Optic Atrophy Sequencing Panel
Periventricular Heterotopia with Microcephaly via the ARFGEF2 Gene
Progressive Myoclonic Epilepsy via the GOSR2 Gene
Progressive Myoclonic Epilepsy, With or Without Renal Failure, via the SCARB2 Gene
Pyridoxine 5'-Phosphate Oxidase Deficiency via the PNPO Gene
Pyridoxine-Dependent Epilepsy via the ALDH7A1 Gene
Retinitis Pigmentosa (includes RPGR ORF15) Sequencing Panel with CNV Detection
Rett Syndrome, Angelman Syndrome and Variant Syndromes Sequencing Panel with CNV Detection
Spinocerebellar Ataxia-12 via the WWOX Gene


Genetic Counselors
  • Carvill GL, Heavin SB, Yendle SC, McMahon JM, O’Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC. 2013. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nature Genetics 45: 825–830. PubMed ID: 23708187
  • Lemke JR, Riesch E, Scheurenbrand T, Schubach M, Wilhelm C, Steiner I, Hansen J, Courage C, Gallati S, Bürki S, Strozzi S, Simonetti BG, Grunt S, Steinlin M, Alber M, Wolff M, Klopstock T, Prott EC, Lorenz R, Spaich C, Rona S, Lakshminarasimhan M, Kröll J, Dorn T, Krämer G, Synofzik M, Becker F, Weber YG, Lerche H, Böhm D, Biskup S. 2012. Targeted next generation sequencing as a diagnostic tool in epileptic disorders: Epilepsy Panel. Epilepsia 53: 1387–1398. PubMed ID: 22612257
  • Mefford HC, Yendle SC, Hsu C, Cook J, Geraghty E, McMahon JM, Eeg-Olofsson O, Sadleir LG, Gill D, Ben-Zeev B, Lerman-Sagie T, Mackay M, Freeman JL, Andermann E, Pelakanos JT, Andrews I, Wallace G, Eichler EE, Berkovic SF, Scheffer IE. 2011. Rare copy number variants are an important cause of epileptic encephalopathies. Annals of Neurology 70: 974–985. PubMed ID: 22190369
  • Mina ED, Ciccone R, Brustia F, Bayindir B, Limongelli I, Vetro A, Iascone M, Pezzoli L, Bellazzi R, Perotti G, Giorgis V De, Lunghi S, et al. 2014. Improving molecular diagnosis in epilepsy by a dedicated high-throughput sequencing platform. European Journal of Human Genetics. PubMed ID: 24848745
  • Noh GJ, Jane Tavyev Asher Y, Graham JM. 2012. Clinical review of genetic epileptic encephalopathies. European Journal of Medical Genetics 55: 281–298. PubMed ID: 22342633
  • Sharma S, Prasad AN. 2013. Genetic Testing of Epileptic Encephalopathies of Infancy: An Approach. The Canadian Journal of Neurological Sciences 40: 10–16. PubMed ID: 23250121
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.
loading Loading... ×