Idiopathic Generalized and Focal Epilepsy Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

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.

Genes in the Idiopathic Generalized and Focal Epilepsy Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ALDH7A1Epilepsy, pyridoxine-dependentAR29110
AMACRAlpha-methylacyl-CoA racemase deficiency, Bile acid synthesis defectAR313
CACNA1HChildhood absence epilepsyAD449
CACNB4Episodic ataxiaAD16
CASRHypocalcemia, Neonatal hyperparathyroidism, Familial Hypocalciuric hypercalcemia with transient Neonatal hyperparathyroidismAD/AR78392
CHRNA2Epilepsy, nocturnal frontal lobeAD111
CHRNA4Epilepsy, nocturnal frontal lobeAD823
CHRNB2Epilepsy, nocturnal frontal lobeAD812
CLCN2Leukoencephalopathy with ataxia, EpilepsyAD/AR1829
DEPDC5Epilepsy, familial focal, with variable fociAD5068
EFHC1Epilepsy, myoclonic juvenile, Epilepsy, severe intractable, Epilepsy, juvenile absenceAD/AR317
GABRA1Epileptic encephalopathy, early infantile, Epilepsy, childhood absence, Epilepsy, juvenile myoclonicAD1535
GABRB3Epilepsy, childhood absenceAD546
GABRG2Generalized epilepsy with febrile seizures plus, Familial febrile seizures, Dravet syndrome, Epilepsy, childhood absenceAD2123
GRIN2AEpilepsy, focal, with speech disorderAD3775
KCNA1Episodic ataxia/myokymia syndromeAD2037
KCNC1Epilepsy, progressive myoclonicAD11
KCNQ2Epileptic encephalopathy, early infantile, Benign familial neonatal seizures, MyokymiaAD240205
KCNQ3Seizures, benign neonatalAD1117
KCNT1Epilepsy, nocturnal frontal lobeAD1628
LGI1Epilepsy, familial temporal lobeAD1948
MTORSmith-Kingsmore syndromeAD710
PRRT2Episodic kinesigenic dyskinesiaAD3291
RELNLissencephaly, Epilepsy, familial temporal lobeAD/AR1731
SCN1AMigraine, familial hemiplegic, Epileptic encephalopathy, early infantile, Generalized epilepsy with febrile seizures plusAD4761282
SCN1BAtrial fibrillation, Brugada syndrome, Generalized epilepsy with febrile seizures plusAD1118
SCN2AEpileptic encephalopathy, early infantile, Seizures, benign familial infantileAD86131
SCN8ACognitive impairment, Epileptic encephalopathy, early infantileAD5655
SCN9AParoxysmal extreme pain disorderAD/AR34102
SLC2A1Stomatin-deficient cryohydrocytosis with neurologic defects, Epilepsy, idiopathic generalized, GLUT1 deficiency syndromeAD/AR65253
SLC6A1Myoclonic-astastic epilepsyAD612
STX1BGeneralized epilepsy with febrile seizures plusAD79
TBC1D24Deafness, Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndromeAD/AR2741

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.

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
Download PDF

Full service only

Choose an analysis method

$ $ 1700
$ $ 1000
$ $ 1900

Extra services

Total $
Order now

ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479


ICD codes

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

ICD-10Disease
G40.00Focal 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