Idiopathic Generalized and Focal Epilepsy Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: NE1101

The Blueprint Genetics Idiopathic Generalized and Focal Epilepsy Panel is a 33 gene test for genetic diagnostics of patients with clinical suspicion of focal epilepsy or generalized epilepsy.

Broadly, the epilepsies are divided clinically into generalised and focal forms. Genetic factors contribute to both and several monogenic diseases have been detected. Causative mutations in many genes, including some genes coding for ion channel subunits and others involved in synaptic function or brain development, have been identified especially during the past few years. Most of these mutations are inherited in an autosomal dominant manner often with incomplete penetrance. The newly designated genetic epilepsies are a heterogenous group. In those patients with known genetic mutations, a significant degree of phenotypic variation and penetrance can be present. Various different epilepsy syndromes may occur within the same family, despite the same genetic mutation. Clinical features and EEG findings, used to define the electroclinical epilepsy syndrome, continues to be a valuable way to classify these disorders in regards to prognosis and treatment. However, genetic diagnosis is needed to fully understand the disease mechanism and it may have an effect to the treatment options. This panel is part of the Comprehensive Epilepsy Panel.

About Idiopathic Generalized and Focal Epilepsy

The idiopathic/genetic generalized epilepsies, characterized by generalized seizures that involve both sides of the cerebrum, include juvenile myoclonic epilepsy and childhood absence epilepsy among others. These generalized epilepsies tend to start in childhood or adolescence and are usually associated with normal development and intellect. Focal seizures originate in one cerebral hemisphere. Examples of focal epilepsy syndromes are temporal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy, and autosomal dominant epilepsy with auditory features.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal

Genes in the Idiopathic Generalized and Focal Epilepsy Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ALDH7A1 Epilepsy, pyridoxine-dependent AR 29 110
AMACR Alpha-methylacyl-CoA racemase deficiency, Bile acid synthesis defect AR 3 13
CACNA1H Childhood absence epilepsy AD 4 49
CACNB4 Episodic ataxia AD 1 6
CASR Hypocalcemia, Neonatal hyperparathyroidism, Familial Hypocalciuric hypercalcemia with transient Neonatal hyperparathyroidism AD/AR 78 392
CHRNA2 Epilepsy, nocturnal frontal lobe AD 1 11
CHRNA4 Epilepsy, nocturnal frontal lobe AD 8 23
CHRNB2 Epilepsy, nocturnal frontal lobe AD 8 12
CLCN2 Leukoencephalopathy with ataxia, Epilepsy AD/AR 18 29
DEPDC5 Epilepsy, familial focal, with variable foci AD 50 68
EFHC1 Epilepsy, myoclonic juvenile, Epilepsy, severe intractable, Epilepsy, juvenile absence AD/AR 3 17
GABRA1 Epileptic encephalopathy, early infantile, Epilepsy, childhood absence, Epilepsy, juvenile myoclonic AD 15 35
GABRB3 Epilepsy, childhood absence AD 5 46
GABRG2 Generalized epilepsy with febrile seizures plus, Familial febrile seizures, Dravet syndrome, Epilepsy, childhood absence AD 21 23
GRIN2A Epilepsy, focal, with speech disorder AD 37 75
KCNA1 Episodic ataxia/myokymia syndrome AD 20 37
KCNC1 Epilepsy, progressive myoclonic AD 1 1
KCNQ2 Epileptic encephalopathy, early infantile, Benign familial neonatal seizures, Myokymia AD 240 205
KCNQ3 Seizures, benign neonatal AD 11 17
KCNT1 Epilepsy, nocturnal frontal lobe AD 16 28
LGI1 Epilepsy, familial temporal lobe AD 19 48
MTOR Smith-Kingsmore syndrome AD 7 10
PRRT2 Episodic kinesigenic dyskinesia AD 32 91
RELN Lissencephaly, Epilepsy, familial temporal lobe AD/AR 17 31
SCN1A Migraine, familial hemiplegic, Epileptic encephalopathy, early infantile, Generalized epilepsy with febrile seizures plus AD 476 1282
SCN1B Atrial fibrillation, Brugada syndrome, Generalized epilepsy with febrile seizures plus AD 11 18
SCN2A Epileptic encephalopathy, early infantile, Seizures, benign familial infantile AD 86 131
SCN8A Cognitive impairment, Epileptic encephalopathy, early infantile AD 56 55
SCN9A Paroxysmal extreme pain disorder AD/AR 34 102
SLC2A1 Stomatin-deficient cryohydrocytosis with neurologic defects, Epilepsy, idiopathic generalized, GLUT1 deficiency syndrome AD/AR 65 253
SLC6A1 Myoclonic-astastic epilepsy AD 6 12
STX1B Generalized epilepsy with febrile seizures plus AD 7 9
TBC1D24 Deafness, Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome AD/AR 27 41

*Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist

 

This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.

 

This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)

 

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a comprehensive Idiopathic Generalized and Focal Epilepsy Panel that covers classical genes associated with focal epilepsy and generalized epilepsy. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

Find more info in Support

Choose an analysis method

$ $ 1700
$ $ 1000
$ $ 1900
Total $
Order now

ICD & CPT codes

CPT codes

SEQ 81479
DEL/DUP 81479


ICD codes

Commonly used ICD-10 codes when ordering the Idiopathic Generalized and Focal Epilepsy Panel

ICD-10 Disease
G40.00 Focal epilepsy

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

Subscribe to our newsletter