Epileptic Encephalopathy Panel

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General Information

Lab Name
Epileptic Encephalopathy Panel
Lab Code
EPIPX
ORCA Name
Epileptic Encephalopathy Panel
Description

Epileptic Encephalopathy Panel is useful for the evaluation of patients with a suspected hereditary epilepsy syndrome. The panel (version 2) uses next-generation sequencing to detect most mutations in ALDH5A1, ALDH7A1, ALG13, ARHGEF9, ARX, CACNA1A, CDKL5, CHD2, CHRNA2, CHRNA4, CHRNA7, CHRNB2, CYFIP1, DEPDC5, DNM1, EEF1A2, FOXG1, GABRA1, GABRB1, GABRB3, GABRG2, GNAO1, GRIN1, GRIN2A, GRIN2B, HCN1, HNRNPU, IQSEC2, KANSL1, KCNA2, KCNB1, KCNH1, KCNH5, KCNQ2, KCNQ3, KCNT1, LGI1, MBD5, MECP2, MEF2C, MTOR, NDE1, PCDH19, PIGA, PLCB1, PNKP, PNPO, POLG, PTEN, PURA, SCN1A, SCN1B, SCN2A, SCN8A, SIK1, SLC13A5, SLC1A2, SLC25A22, SLC2A1, SLC35A2, SLC6A1, SLC9A6, SPTAN1, STX1B, STXBP1, SYN1, SYNGAP1, TBC1D24, TCF4, TSC1, TSC2, UBE3A, WDR45, WWOX, and ZEB2. The assay completely sequences all exons of these genes AND detects large deletions, duplications and mosaicism. For patients with suspected megalencephaly or overgrowth syndrome, see Megalencephaly Panel [MEGPX].

Gene Disease Reference (PMID)
ALDH5A1 Succinic semialdehyde dehydrogenase deficiency 20301374
ALDH7A1 Pyridoxine-Dependent Epilepsy 20301659
ALG13 Epileptic encephalopthy, girls 23934111
ARHGEF9 X linked intellectual disability and hyperekplexia, Borjeson-Frossman-Lehmann syndrome 21633362
ARX Epilepsy, infantile spasms, Lennox-Gastaut syndrome, Lissencephaly, agenesis of the corpus callosum 14722918
CACNA1A Epileptic encephalopathy, hemiplegic migraine 11342703
CDKL5 Severe early onset epileptic encephalopathy - usually girls, boys even more severely affected (X-linked) 12736870
CHD2 CHD2-related neurodevelopmental disorders, early onset epileptic encephalopathy, photosensitive epilepsy, eyelid myoclonus 26677509,23708187
CHRNA2 ADNFLE, focal epilepsy 20301348
CHRNA4 ADNFLE, focal epilepsy 20301348
CHRNA7 15q13.3 recurrent microdeletion syndrome, risk factor for idiopathic generalized epilepsy and neurodevelopmental disorders 21290787,20502679
CHRNB2 ADNFLE, focal epilepsy 20301348
CYFIP1 15q11.2 recurrent microdeletion syndrome, risk factor for idiopathic generalized epilepsy and neurodevelopmental disorders 19843651,20502679
DEPDC5 Focal epilepsy with or without focal cortical dysplasia; familal focal epilepsy with variable foci 23542701,23542697
DNM1 Epileptic encephalopathy 25262651
EEF1A2 Epileptic encephalopathy, early myoclonic epilepsy 23647072,24697219,26682508
FOXG1 Congenital variant Rett syndrome 24836831
GABRA1 Dravet, Ohtahara, West syndrome; generalized epilepsy 24623842,26918889
GABRB1 Epileptic encephalopathy
GABRB3 Epileptic encephalopathy 23934111,26645412
GABRG2 Epileptic encephalopathy, Dravet-like 11326275
GNAO1 Epileptic encephalopathy 23993195
GRIN1 Early infantile epileptic encephalopathy 25864721,26933583
GRIN2A Epilepsy aphasia syndromes 23933818,23933819,23933820
GRIN2B Epileptic encephalopathy, infantile spasms, autism 24272827
HCN1 Epileptic encephalopathy, Dravet-like 24747641
HNRNPU Early infantile epileptic encephalopathy 23934111
IQSEC2 Non-syndromic X linked intellectual disability, epileptic encephelopathy, variant Rett syndrome 20473311,23934111,23674175
KANSL1 Koolen-de Vries (17q21 deletion) syndrome 22544363,22544367
KCNA2 Epileptic encephalopathy; myoclonic epilepsy with ataxia 25751627
KCNB1 Epileptic encephalopathy 25164438
KCNH1 Temple-Baraitser syndrome 25420144
KCNH5 Epilepsy aphasia syndromes; epileptic encephalopathy 23647072
KCNQ2 Benign familial infantile seizures; epileptic encephalopathy 9425895,20437616
KCNQ3 Benign familial infantile seizures 9425900
KCNT1 Epilepsy with migrating focal seizures in infancy (EMFSI), epileptic encephalopathy, autosomal dominant nocturnal frontal lobe epilepsy 23086396,23086397,26122718,26140313
LGI1 Autosomal dominant partial epilepsy with auditory features (ADPEAF) 20301709
MBD5 Severe ID + epilepsy, most are deletions 23587880
MECP2 Rett syndrome 20301670
MEF2C Infatile spasms/encephalopathy 23389741
MTOR Megalencephaly, hemimegalencephaly, focal cortical dysplasia 25799227
NDE1 Lissencephaly with microcephaly (AR), plus deletion a risk factor for generalized epilepsy 21529751
PCDH19 Epilepsy in females with mental retardation (EFMR), now called girls' clustering epilepsy 18469813,19214208
PIGA Early infantile epileptic encephalopathy, ferro-cerebro-cutaneous syndrome 26993267,24259288,24706016
PLCB1 Epilepsy with migrating focal seizures in infancy (EMFSI); epileptic encephalopathy; AR inheritance, deletions reported 22690784,26818157
PNKP Ataxia with Oculomotor Apraxia 4 / syndrome of microcephaly, seizures, and developmental delay / progressive cerebellar atrophy and polyneuropathy 25728773,23224214,20118933
PNPO PNPO deficieny, neonatal epileptic encephalopathy 24645144
POLG POLG-related disorders: mitochondrial DNA depletion syndromes, Alpers-Huttenlocher, progressive external ophthalmoplegia, Myoclonic epilepsy myopathy sensory ataxia (MEMSA) 20301791
PTEN Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome (BRRS) PTEN related hamartoma syndrome, autism, focal cortical dysplasia 20301661
PURA Epileptic encephalopathy 25342064,25439098
SCN1A Dravet syndrome, GEFS+ 20301494
SCN1B Early infantile epileptic encephalopathy 9697698
SCN2A Epileptic encephalopathy 11738931
SCN8A Epileptic encephalopathy 25568300,22365152
SIK1 Early onset epilepsy 25839329
SLC13A5 Autosomal recessive early onset epilepsy 24995870
SLC1A2 Epileptic encephalopathy pending
SLC25A22 Early onset epileptic encephalopathy 21967765
SLC2A1 GLUT1 deficiency syndrome 20301603
SLC35A2 Early onset epilepsy 24115232
SLC6A1 Myoclonic atonic epilepsy (MAE) 25865495
SLC9A6 Christianson syndrome; X-linked Angelman-like condition 22541666,24630051
SPTAN1 Epilepsy, infantile spasms, intellectual disability 25631096
STX1B Fever-associated epilepsies; Dravet-like 25362483
STXBP1 Otahara syndrome, early infantile epileptic encephalopathy (EIEE) 26865513
SYN1 Epilepsy, autism 14985377,21441247
SYNGAP1 Epileptic encephalopathy 23708187,26989088
TBC1D24 TBC1D24 related disorders: Deafness, Onychodystrophy, Osteodystrophy, mental Retardation, Seizures (DOORS), familial infantile myoclonic epilepsy 25719194
TCF4 Pitt Hopkins syndrome 22934316
TSC1 Tuberous Sclerosis 20301399
TSC2 Tuberous Sclerosis 20301399
UBE3A Angelman syndrome 20301323
WDR45 X linked neurodegeneration with brain iron accumulation (NBIA), static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), 23687123,23447832,23435086
WWOX Early infantile epileptic encephalopathy, autosomal recessive spinocerebellar ataxia 12 25411445,24369382
ZEB2 Mowat Wilson syndrome 20301585

For previous versions of EpiPlex™ - Epileptic Encephalopathy Panel, see Previous Versions, EPIPX.

References
  • Pritchard CC, et al. ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 2012, 14:357-66. 22658618
  • Walsh T, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A 2010, 107:12629-33. 20616022
  • Nord AS, Lee M, King MC, and Walsh T. Accurate and exact CNV identification from targeted high-throughput sequence data. BMC Genomics 2011, 12:184. 21486468
  • Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010, 11:31-46. 19997069
Forms & Requisitions

Requisition Form and Ordering Instructions:

1. Fill out a Genetics Requisition Form

2. Check "Epileptic Encephalopathy Panel"

Genetics Preauthorization Form (preauthorization is only done for providers who are external to the UW system).

Synonyms
ALDH5A1, ALDH7A1, ALG13, ARHGEF9, ARX, CACNA1A, CDKL5, CHD2, CHRNA2, CHRNA4, CHRNA7, CHRNB2, CYFIP1, DEPDC5, DNM1, EEF1A2, FOXG1, GABRA1, GABRB1, GABRB3, GABRG2, GNAO1, GRIN1, GRIN2A, GRIN2B, HCN1, HNRNPU, IQSEC2, KANSL1, KCNA2, KCNB1, KCNH1, KCNH5, KCNQ2, KCNQ3, KCNT1, LGI1, MBD5, MECP2, MEF2C, MTOR, NDE1, PCDH19, PIGA, PLCB1, PNKP, PNPO, POLG, PTEN, PURA, SCN1A, SCN1B, SCN2A, SCN8A, SIK1, SLC13A5, SLC1A2, SLC25A22, SLC2A1, SLC35A2, SLC6A1, SLC9A6, SPTAN1, STX1B, STXBP1, SYN1, SYNGAP1, TBC1D24, TCF4, TSC1, TSC2, UBE3A, WDR45, WWOX, ZEB2, hereditary encephalopathy, hereditary epilepsy, hereditary seizures, next-generation sequencing
Components

Interpretation

Method

Next-generation sequencing

Reference Range
See individual components
Ref. Range Notes

No mutations detected.

References
  • Pritchard CC, et al. ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 2012, 14:357-66. 22658618
  • Walsh T, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A 2010, 107:12629-33. 20616022
  • Nord AS, Lee M, King MC, and Walsh T. Accurate and exact CNV identification from targeted high-throughput sequence data. BMC Genomics 2011, 12:184. 21486468
  • Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010, 11:31-46. 19997069
Guidelines

Ordering & Collection

Specimen Type
Peripheral Blood, cultured cells from skin biopsy, purified DNA from peripheral blood or cultured cells
Collection

BLOOD:

  • 10 mL whole blood in LAVENDER TOP EDTA tube.
  • Also acceptable: YELLOW TOP ACD tube, purified DNA from peripheral blood or cultured cells.

SKIN BIOPSY:

  • Collection and transport: Obtain 2-4 mm punch biopsy of skin sample under sterile conditions and place in transport media (e.g. Alpha-MEM media, RPMI). Transport media can be supplied by the lab; call 206-598-4488 to request. If transport media is not available, the following media are acceptable alternatives if shipping time will not exceed 24 hours: lactated Ringer's solution, viral transport medium, or sterile saline. DO NOT USE formaldehyde, formalin, alcohol, or 5% dextrose, or tissue culture medium buffered with bicarbonate.

CULTURED CELLS:

  • (2) T23 or (1) T75 flask (minimum 1-T25 flask)*.

*Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide [[MCC]] for ordering and specimen requirements)

Forms & Requisitions

Requisition Form and Ordering Instructions:

1. Fill out a Genetics Requisition Form

2. Check "Epileptic Encephalopathy Panel"

Genetics Preauthorization Form (preauthorization is only done for providers who are external to the UW system).

Handling Instructions

Ship specimen at room temperature for overnight delivery.

Blood specimens can be held for up to 7 days before shipping if refrigerated.

Ship specimens to:

UW MEDICAL CENTER

LABORATORY MEDICINE - GENETICS LAB

1959 NE PACIFIC ST, ROOM NW220

SEATTLE, WA 98195-7110

Quantity
requested: Entire sample
minimum: 5 mL whole blood

Processing

Processing

Blood: Refrigerate whole blood

Unacceptable Conditions: Frozen or clotted specimens

Stability (collection to initiation of testing): Ambient: 5 days; Refrigerated: 7 days; Frozen: Unacceptable

Purified DNA: Refrigerate DNA specimens. Frozen is acceptable.

Performance

LIS Dept Code
Genetics (GEN)
Performing Location(s)
UW-MT Genetics

Attention: Genetics Lab
Clinical lab, Room NW220
University of Washington Medical Center
1959 NE Pacific Street
Seattle, WA 98195

Tel: 206-598–6429 M–F (7:30 AM–4:00 PM)
Fax: 206-598–0304
Lab email: genelab@uw.edu

Supervisor

Robert Livingston, PhD bobl@uw.edu

Genetic Counselors

Angela Jacobson, MS, LGC agibson@uw.edu
Sarah Paolucci, MA, MS, LGC, spaolucc@uw.edu
Jenna Huey, MS, LGC, jlhuey@uw.edu

Faculty

Colin C. Pritchard, MD, PhD
Brian H. Shirts, MD, PhD
Christina Lockwood, PhD, DABCC
Stephen Salipante, MD, PhD
Eric Konnick, MD, MS
Karen Stephens, PhD, FACMG
Jonathan F. Tait, MD, PhD
Vera Paulson, MD, PhD
Jillian Buchan, PhD, FACMG

Frequency
Results within 4 weeks, once sample arrives in the laboratory.
Available STAT?
No

Billing & Coding

CPT codes
Billing Comments

For additional test/billing information, see following page: Epileptic Encephalopathy CPT codes.

For pricing information, contact Client Support Services 206-520-4600 or 800-713-5198.

Billing and Insurance Pre-Authorization

We offer insurance pre-authorization services (preauthorization is only done for providers who are external to the UW system).

Email: ngsbill@uw.edu or call 1-855-320-4869 for more information.

Genetics Preauthorization Form

LOINC