Early Infantile Epileptic Encephalopathy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesGene CPT Codes Copy CPT Codes
10429 ACY181479,81479 Add to Order
ADSL81479,81479
ALDH7A181406,81479
ARFGEF281479,81479
ARHGEF981479,81479
ARX81404,81403
BCKDK81479,81479
CDKL581406,81405
CHD281479,81479
CHRNA281479,81479
CHRNA481405,81479
CHRNB281405,81479
CLN381479,81479
CLN581479,81479
CLN681479,81479
CLN881479,81479
CNTNAP281406,81479
CSTB81189,81479
CTSD81479,81479
CTSF81479,81479
DEPDC581479,81479
EPM2A81404,81479
FARS281479,81479
FOLR181479,81479
FOXG181404,81479
GABRA181479,81479
GABRB381479,81479
GABRG281405,81479
GAMT81479,81479
GNAO181479,81479
GOSR281479,81479
GRIN2A81479,81479
HCN181479,81479
KCNA281479,81479
KCNB181479,81479
KCNJ1081404,81479
KCNQ281406,81479
KCNQ381479,81479
KCNT181479,81479
KCTD781479,81479
LGI181479,81479
MBD581479,81479
MECP281302,81304
MEF2C81479,81479
MFSD881479,81479
NHLRC181403,81479
NPRL281479,81479
NRXN181479,81479
PCDH1981405,81479
PIGO81479,81479
PLCB181479,81479
PNKP81479,81479
PNPO81479,81479
POLG81406,81479
PPT181479,81479
PRRT281479,81479
RELN81479,81479
ROGDI81479,81479
SCARB281479,81479
SCN1A81407,81479
SCN1B81404,81479
SCN2A81479,81479
SCN8A81479,81479
SCN9A81479,81479
SLC13A581479,81479
SLC19A381479,81479
SLC25A2281479,81479
SLC2A181405,81479
SLC35A281479,81479
SLC9A681406,81479
SPTAN181479,81479
ST3GAL381479,81479
ST3GAL581479,81479
STX1B81479,81479
STXBP181406,81479
SZT281479,81479
TBC1D2481479,81479
TNK281479,81479
TPP181479,81479
TSC181406,81405
TSC281407,81406
WWOX81479,81479
Test Code Test Copy Genes Total Price Panel CPT Code Gene CPT Codes Copy CPT Code
10429 Genes x (82) $990 81479 81189, 81302, 81304, 81403, 81404, 81405, 81406, 81407, 81479 Add to Order

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel 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 via our PGxome Custom Panel tool.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

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. PubMed ID: 22342633). 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, such as the characteristic burst-suppression pattern seen in Ohtahara syndrome (Khan and Al Baradie 2012. PubMed ID: 23213494). Intellectual disability and psychomotor delay are common features of many severe epileptic encephalopathies.

Genetics

The most common causes of EIEE in infants are structural brain abnormalities and inborn errors of metabolism (Sharma and Prasad 2013. PubMed ID: 23250121, Wilmshurst et al. 2015. PubMed ID: 26122601). 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; over 100 genes have been suggested to be involved in disease pathogenesis (Lemke et al. 2012. PubMed ID: 22612257). Many EIEE cases are sporadic, occurring in families with no prior history of seizure (Allen et al. 2013. PubMed ID: 23934111). Sporadic cases of EIEE are commonly caused by dominant, de novo pathogenic variants in neuronally expressed genes. EIEE can also be inherited in an autosomal recessive manner. In this panel, we sequence a total of 82 genes. This panel covers 22 genes which are related to epilepsy treatment including ALDH7A1, BCKDK, CHRNA4, DEPDC5, FOLR1, GAMT,GRIN2A, KCNQ2, KCNQ3, KCNT1, PCDH19, PNPO, POLG, PRRT2, SCN1A, SCN2A, SCN8A, SLC19A3, SLC2A1, STXBP1, TSC1 and TSC2 (see the table below).

41 genes in which dominant or X-linked pathogenic variants have been reported in the literature to be causative for EIEE. Several of these genes are involved in well-characterized syndromes in which seizures are a predominant feature (Ottman et al. 2010. PubMed ID: 20100225; Wilmshurst et al. 2015. PubMed ID: 26122601) such as:

Tuberous Sclerosis: TSC1 and TSC2

Infantile Spasm: ADSL, ARX, CDKL5, PNPO, MEF2C, SCN1A, SCN2A, STXBP1, TSC1, TSC2

Focal epilepsy: CHRNA4, CHRNB2, CHRNA2, CNTNAP2, DEPDC5, KCNT1, GRIN2A, LGI1, NPRL2, PCDH19, RELN, SCN1A, TBC1D24

Dravet Syndrome: SCN1A, SCN1B, GABRG2, SCN2A, SCN9A, PCDH19, GABRA1, STXBP1 and CHD2.

Ohtahara Syndrome: ARX, STXBP1, SCN2A, KCNQ2, KCNT1, SLC25A22, CDKL5, PNKP and SPTAN1.

Generalized (or genetic) Epilepsy with Febrile Seizures Plus (GEFS+): SCN1A, SCN1B, SCN2A, SCN9A), GABRG2, STX1B

DEPDC5-related epilepsy

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy: CHRNA4, CHRNB2, CHRNA2, DEPDC5, KCNT1

Autosomal Dominant Lateral Temporal Lobe Epilepsy: LGI1, RELN

Benign Familial Neonatal or Infantile Seizures: KCNQ2, KCNQ3, PRRT2

Early-onset Absence Epilepsy: SLC2A1

Epilepsy and Mental Retardation Limited to Females: PCDH19

Rett Syndrome: MECP2, CDKL5, FOXG1

41 genes in which homozygous or compound heterozygous pathogenic variants have been reported to cause EIEE. Some of these genes are involved in well-characterized autosomal recessive conditions in which seizures are a predominant feature such as:

Neuronal Ceroid Lipofuscinosis: TPP1, PPT1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSF and KCTD7

Lafora Disease: EPM2A and NHLRC1

Selected metabolic disorders: FOLR1, GAMT, ALDH7A1, PNPO, SLC19A3

Selected mitochondrial disease: POLG, FARS2, SLC25A22

Gene Name Inherited Mode Treatment Related References
ALDH7A1 AR Bennett et al. 2009. PubMed ID: 19128417
BCKDK AR Oyarzabal et al. 2016. PubMed ID: 26809120
CHRNA4 AD Kurahashi and Hirose 2015. PubMed ID: 20301348
DEPDC5 AD Myers and Scheffer 2017. PubMed ID: 28406046
FOLR1 AR Steinfeld et al. 2009. PubMed ID: 19732866
GAMT AR Bodamer et al. 2009. PubMed ID: 19255414
GRIN2A AD Pierson et al 2014. PubMed ID: 24839611
KCNQ2 AD Sands et al. 2016. PubMed ID: 27888506
KCNQ3 AD Sands et al. 2016. PubMed ID: 27888506
KCNT1 AD Mikati et al 2015. PubMed ID: 26369628
PCDH19 AD Trivisano et al 2015. PubMed ID: 25510386
PNPO AR Bagci et al. 2007. PubMed ID: 18296573
POLG AR Hynynen et al 2014. PubMed ID: 25065347
PRRT2 AD Chou et al 2014. PubMed ID: 25520928
SCN1A AD Miller and Sotero de Menezes 2007. PubMed ID: 20301494.
SCN2A AD Wolff et al 2017. PubMed ID: 28379373
SCN8A AD Boerma et al 2016. PubMed ID: 26252990
SLC19A3 AR Tabarki et al. 2013. PubMed ID: 23269594
SLC2A1 AD Leen et al. 2010. PubMed ID: 20129935
STXBP1 AD Dilena et al 2016. PubMed ID: 26212315
TSC1 AD Palavra et al 2017. PubMed ID: 28386314
TSC2 AD Palavra et al 2017. PubMed ID: 28386314

See individual gene test descriptions for information on molecular biology of gene products and spectra of pathogenic variants.

Testing Strategy

This panel typically provides ≥98% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV

This panel includes genes causative for autosomal dominant, autosomal recessive and X-linked early infantile epileptic encephalopathy (EIEE). Extrapolating from previously published studies of next generation sequencing in large cohorts of patients with EIEE, we predict that our EIEE Panel will identify pathogenic variants more than 37% of EIEE cases with unknown cause (Lemke et al. 2012. PubMed ID: 22612257; Kodera et al. 2013. PubMed ID: 23662938; Carvill et al. 2013. PubMed ID: 23708187; Della Mina et al. 2015. PubMed ID: 24848745; Wang et al. 2014. PubMed ID:24818677; Ream et al. 2014. PubMed ID:25108116). In particular, clinical sensitivity for Autosomal Dominant Nocturnal Frontal Lobe Epilepsy is more than 25-35% while for autosomal dominant focal epilepsy, the sensitivity is more than 12-37% (Dibbens et al. 2013. PubMed ID:23542697; Ishida et al. 2013. PubMed ID:23542701; Picard et al. 2014. PubMed ID:24814846). This panel identifies pathogenic variants in 70-80% of Dravet syndrome patients (Ottman et al 2010. PubMed ID:20100225; Carvill et al 2014. PubMed ID:24623842; Gaily et al 2013. PubMed ID:23808377).

Large deletions or duplications that may not be detectable by sequencing have been reported in ARHGEF9, ARX, CDKL5, CHD2, FOXG1, GABRA1, GABRB3, GABRG2, GRIN2A, LGI1, MBD5, MECP2, MEF2C, PCDH19, PRRT2, SCN1A, SCN2A, SCN8A, SLC2A1, SLC9A6, SPTAN1, STX1B, STXBP1, TSC1 and TSC2 (Human Gene Mutation Database). Patients with an identifiable TSC pathogenic variant will have either a large deletion or duplication in up to 6% and 1% of cases in the TSC2 and TSC1 genes, respectively (Northrup et al. 2015. PubMed ID:20301399).

Indications for Test

Testing is recommended for patients with symptoms of EIEE, notably those with infantile onset seizures with no clear structural or metabolic cause.

Diseases

Name Inheritance OMIM ID
Aminoacylase 1 Deficiency AR 609924
Amish Infantile Epilepsy Syndrome AR 609056
Basal Ganglia Disease, Biotin-Responsive AR 607483
Branched-chain ketoacid dehydrogenase kinase deficiency AR 614923
Cerebral Folate Deficiency AR 613068
Ceroid Lipofuscinosis Neuronal 1 AR 256730
Ceroid Lipofuscinosis Neuronal 10 AR 610127
Ceroid Lipofuscinosis Neuronal 13 AR 615362
Ceroid Lipofuscinosis Neuronal 2 AR 204500
Ceroid Lipofuscinosis Neuronal 3 AR 204200
Ceroid Lipofuscinosis Neuronal 4A, Autosomal Recessive AR 204300
Ceroid Lipofuscinosis Neuronal 5 AR 256731
Ceroid Lipofuscinosis Neuronal 6 AR 601780
Ceroid Lipofuscinosis Neuronal 7 AR 610951
Ceroid Lipofuscinosis Neuronal 8 AR 600143
Ceroid Lipofuscinosis Neuronal 8, Northern Epilepsy Variant AR 610003
Congenital Disorder of Glycosylation Type IIm XL 300896
Cortical Dysplasia-Focal Epilepsy Syndrome AR 610042
Epilepsy, familial focal, with variable foci AD 604364
Epilepsy, Familial Focal, with Variable Foci 2 AD 617116
Epilepsy, Familial Temporal Lobe, 7 AD 616436
Epilepsy, focal, with speech disorder and with or without mental retardation AD 245570
Epilepsy, Lateral Temporal Lobe, Autosomal Dominant AD 600512
Epilepsy, Nocturnal Frontal Lobe, Type 1 AD 600513
Epilepsy, Nocturnal Frontal Lobe, Type 3 AD 605375
Epilepsy, Nocturnal Frontal Lobe, Type 4 AD 610353
Epilepsy, Progressive Myoclonic 3 AR 611726
Epilepsy, Progressive Myoclonic 4, With Or Without Renal Failure AR 254900
Epilepsy, Progressive Myoclonic 6 AR 614018
Epileptic encephalopathy, childhood-onset AD 615369
Epileptic encephalopathy, early infantile, 1 XL 308350
Epileptic Encephalopathy, Early Infantile, 10 AR 613402
Epileptic Encephalopathy, Early Infantile, 11 AD 613721
Epileptic Encephalopathy, Early Infantile, 12 AR 613722
Epileptic Encephalopathy, Early Infantile, 13 AD 614558
Epileptic encephalopathy, early infantile, 14 AD 614959
Epileptic Encephalopathy, Early Infantile, 15 AR 615006
Epileptic Encephalopathy, Early Infantile, 16 AR 615338
Epileptic Encephalopathy, Early Infantile, 17 AD 615473
Epileptic encephalopathy, early infantile, 18 AR 615476
Epileptic Encephalopathy, Early Infantile, 2 XL 300672
Epileptic Encephalopathy, Early Infantile, 24 AD 615871
Epileptic Encephalopathy, Early Infantile, 25 AR 615905
Epileptic Encephalopathy, Early Infantile, 26 AD 616056
Epileptic Encephalopathy, Early Infantile, 3 AR 609304
Epileptic Encephalopathy, Early Infantile, 32 AD 616366
Epileptic Encephalopathy, Early Infantile, 4 AD 612164
Epileptic Encephalopathy, Early Infantile, 5 AD 613477
Epileptic Encephalopathy, Early Infantile, 7 AD 613720
Epileptic Encephalopathy, Early Infantile, 8 XL 300607
Epileptic Encephalopathy, Early Infantile, 9 XL 300088
Generalized Epilepsy With Febrile Seizures Plus, Type 1 AD 604233
Generalized Epilepsy With Febrile Seizures Plus, Type 3 AD 611277
Generalized Epilepsy With Febrile Seizures Plus, Type 7 AD 613863
Generalized Epilepsy with Febrile Seizures Plus, Type 9 AD 616172
Glut1 Deficiency Syndrome 1 AD 606777
Heterotopia, Periventricular, Autosomal Recessive AR 608097
Hyperphosphatasia with mental retardation syndrome 2 AR 614749
Kohlschutter-Tonz syndrome AR 226750
Lafora Disease AR 254780
Mental Retardation, Autosomal Dominant 1 AD 156200
Mental Retardation, Stereotypic Movements, Epilepsy, And/Or Cerebral Malformations AD 613443
Mental Retardation, X-Linked, Syndromic, Christianson Type XL 300243
Myoclonic Epilepsy, Familial Infantile AR 605021
Pitt-Hopkins-like syndrome 2 AR 614325
Progressive Sclerosing Poliodystrophy AR 203700
Pyridoxine-Dependent Epilepsy AR 266100
Rett Syndrome, Congenital Variant IC 613454
Seizures, Benign Familial Infantile, 2 AD 605751
Seizures, Benign Familial Neonatal, 2 AD 121201
SeSAME Syndrome AR 612780
Spinocerebellar ataxia, autosomal recessive 12 AR 614322
Tuberous Sclerosis 1 AD 191100
Tuberous Sclerosis 2 AD 613254
Unverricht-Lundborg Syndrome AR 254800

Related Test

Name
PGxome®

Citations

  • Allen et al. 2013. PubMed ID: 23934111
  • Bagci et al. 2007. PubMed ID: 18296573
  • Bennett et al. 2009. PubMed ID: 19128417
  • Bodamer et al. 2009. PubMed ID: 19255414
  • Boerma et al 2016. PubMed ID: 26252990
  • Carvill et al. 2013. PubMed ID: 23708187
  • Carvill et al. 2014. PubMed ID: 24623842
  • Chou et al 2014. PubMed ID: 25520928
  • Della Mina et al. 2015. PubMed ID: 24848745
  • Dibbens et al. 2013. PubMed ID: 23542697
  • Dilena et al 2016. PubMed ID: 26212315
  • Gaily et al. 2013. PubMed ID: 23808377
  • Human Gene Mutation Database (Bio-base).
  • Hynynen et al 2014. PubMed ID: 25065347
  • Ishida et al. 2013. PubMed ID: 23542701
  • Khan and Al Baradie. 2012. PubMed ID: 23213494
  • Kodera et al. 2013. PubMed ID: 23662938
  • Kurahashi and Hirose 2015. PubMed ID: 20301348
  • Leen et al. 2010. PubMed ID: 20129935
  • Lemke et al. 2012. PubMed ID: 22612257
  • Mikati et al 2015. PubMed ID: 26369628
  • Miller and Sotero de Menezes 2007. PubMed ID: 20301494
  • Myers and Scheffer 2017 PubMed ID: 28406046
  • Noh et al. 2012. PubMed ID: 22342633
  • Northrup et al. 2015. PubMed ID: 20301399
  • Ottman et al. 2010. PubMed ID: 20100225
  • Oyarzabal et al. 2016. PubMed ID: 26809120
  • Palavra et al 2017. PubMed ID: 28386314
  • Picard et al. 2014. PubMed ID: 24814846
  • Pierson et al 2014. PubMed ID: 24839611
  • Ream and Mikati. 2014. PubMed ID: 25108116
  • Sands et al. 2016. PubMed ID: 27888506
  • Sharma and Prasad. 2013. PubMed ID: 23250121
  • Steinfeld et al. 2009. PubMed ID: 19732866
  • Tabarki et al. 2013. PubMed ID: 23269594
  • Trivisano et al 2015. PubMed ID: 25510386
  • Wang et al. 2014. PubMed ID: 24818677
  • Wilmshurst et al. 2015. PubMed ID: 26122601
  • Wolff et al 2017. PubMed ID: 28379373

Ordering/Specimens

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.

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.

Specimen Types

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