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 ADSL81479,81479 Add to Order
Test Code Test Copy Genes Total Price Panel CPT Code Gene CPT Codes Copy CPT Code STAT
10429 Genes x (117) $1240 81479 81185, 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

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


Genetic Counselors


Clinical Features and Genetics

Clinical Features

Early Infantile Epileptic Encephalopathy (EIEE) is a clinically heterogeneous neurodevelopmental disorder. It is characterized by frequent and/or severe seizures within the first 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). Patients with EIEE 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. EIEE is rare; it is estimated to affect 1/100,000 to 1/50,000 live births (orphanet).

Identifying the molecular basis of a patient’s epilepsy may provide valuable information to inform prognosis, recurrence risk, and treatment.  In particular, targeted therapy of genetic epilepsies is an area of rapid change and great promise (see table below). Some patients may benefit from drugs that target a specific pathway, gene product, or functional change to a specific protein (Musto et al. 2020. PubMed ID: 31889633; Reif et al. 2017. PubMed ID: 27781560).


EIEE is genetically heterogeneous; over 100 genes are involved in disease pathogenesis (Lemke et al. 2012. PubMed ID: 22612257). Structural brain abnormalities and inborn errors of metabolism are among the most common comorbidities. However, seizures may be idiopathic or associated with trauma (Sharma and Prasad 2013. PubMed ID: 23250121; Wilmshurst et al. 2015. PubMed ID: 26122601). An increasing fraction of EIEE can be attributed to a genetic cause.  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 may be inherited by autosomal recessive transmission, but are more commonly caused by dominant, de novo, pathogenic variants in neuronally-expressed genes. De novo pathogenic missense variants are especially common among genetic epilepsies. For example, missense variants in ion channels (channelopathies) may modify gating kinetics, ion permeability, voltage sensitivity or ligand-binding imparting both gain- or loss-of-function effects (Kullmann. 2002. PubMed ID: 12023309). In addition, a large number of epilepsy-related genes are sensitive to null mutation and chain-terminating variants that are well-documented to be pathogenic (Human Gene Mutation Database). Finally, rare cases of EIEE have been attributed to copy number changes involving epilepsy-related genes (ARHGEF9, ARX, CDKL5, CHD2, DNM1, FOXG1, GABRA1, GABRB3, GABRG2, GRIN2A, MBD5, MECP2, MEF2C, PCDH19, PLCB1, PRRT2, SCN1A, SCN2A, SCN8A, SLC2A1, SLC9A6, SPTAN1, STX1B, STXBP1, TSC1 and TSC2). This test includes CNV analysis.  

In this panel, we sequence a total of 117 genes. Among them, over 20 genes have been associated with precision therapy in gene-drug studies. These include 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). The panel includes 66 genes listed in OMIM in the phenotypic series of EIEE. Additionally, several genes on this panel are included based on their association with well-characterized syndromes in which infantile seizures are a predominant feature (Ottman et al. 2010. PubMed ID: 20100225; Wilmshurst et al. 2015. PubMed ID: 26122601). Examples of related epilepsy syndromes include:

Tuberous Sclerosis: TSC1 and TSC2

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

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, and STX1B

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

Early-onset Absence Epilepsy: SLC2A1

Rett Syndrome: MECP2, CDKL5, and FOXG1

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

Selected mitochondrial disease: POLG, FARS2, and SLC25A22

Gene Name Inherited Mode Treatment Related References
ALDH7A1 AR Bennett et al. 2009. PubMed ID: 19128417
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 summaries for more information about molecular biology of gene products and spectra of pathogenic variants. 

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 98.3% 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. 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 in 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 and Mikati. 2014. PubMed ID:25108116).

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.


Official Gene Symbol OMIM ID
ADSL 608222
ALDH7A1 107323
ALG13 300776
AP3B2 602166
ARHGEF9 300429
ARX 300382
ATP1A3 182350
BRAT1 614506
CACNA1A 601011
CDKL5 300203
CHD2 602119
CLCN4 302910
CLN8 607837
CNPY3 610774
CNTNAP2 604569
CPLX1 605032
CTSD 116840
CUX2 610648
CYFIP2 606323
DENND5A 617278
DEPDC5 614191
DNM1 602377
DOCK7 615730
EEF1A2 602959
FARS2 611592
FGF12 601513
FOLR1 136430
FOXG1 164874
FRRS1L 604574
GABBR2 607340
GABRA1 137160
GABRB1 137190
GABRB2 600232
GABRB3 137192
GABRG2 137164
GAMT 601240
GLS 138280
GNAO1 139311
GPHN 603930
GRIN1 138249
GRIN2A 138253
GRIN2B 138252
GRIN2D 602717
HCN1 602780
HNRNPU 602869
ITPA 147520
KCNA2 176262
KCNB1 600397
KCNJ10 602208
KCNMA1 600150
KCNQ2 602235
KCNQ3 602232
KCNT1 608167
KCNT2 610044
KCTD7 611725
MAGI2 606382
MBD5 611472
MDH2 154100
MECP2 300005
MEF2C 600662
MFSD8 611124
NGLY1 610661
NPRL3 600928
NRXN1 600565
NTRK2 600456
PACS2 610423
PCDH19 300460
PHACTR1 608723
PIGA 311770
PIGO 614730
PIGP 605938
PIGV 610274
PLCB1 607120
PNKP 605610
PNPO 603287
POLG 174763
PPT1 600722
PRRT2 614386
PURA 600473
RHOBTB2 607352
ROGDI 614574
SCN1A 182389
SCN1B 600235
SCN2A 182390
SCN3A 182391
SCN8A 600702
SCN9A 603415
SLC12A5 606726
SLC13A5 608305
SLC19A3 606152
SLC1A2 600300
SLC25A12 603667
SLC25A22 609302
SLC2A1 138140
SLC35A2 314375
SLC6A1 137165
SLC9A6 300231
SMC1A 300040
SPATA5 613940
SPTAN1 182810
ST3GAL3 606494
ST3GAL5 604402
STX1B 601485
STXBP1 602926
SYNGAP1 603384
SYNJ1 604297
SZT2 615463
TBC1D24 613577
TPP1 607998
TSC1 605284
TSC2 191092
UBA5 610552
UBE3A 601623
WDR45 300526
WWOX 605131
YWHAG 605356
ZEB2 605802
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Adenylosuccinate Lyase Deficiency AR 103050
Alternating Hemiplegia of Childhood 2 AD 614820
Amish Infantile Epilepsy Syndrome AR 609056
Angelman Syndrome AD 105830
Ataxia-oculomotor apraxia 4 AR 616267
Basal Ganglia Disease, Biotin-Responsive AR 607483
Benign Familial Neonatal Seizures 1 AD 121200
Benign Familial Neonatal-Infantile Seizures AD 607745
CAPOS syndrome AD 601338
Cerebellar atrophy, developmental delay, and seizures AR 617643
Cerebral Folate Deficiency AR 613068
Ceroid Lipofuscinosis Neuronal 1 AR 256730
Ceroid Lipofuscinosis Neuronal 10 AR 610127
Ceroid Lipofuscinosis Neuronal 14 AR 611726
Ceroid Lipofuscinosis Neuronal 2 AR 204500
Ceroid Lipofuscinosis Neuronal 7 AR 610951
Ceroid Lipofuscinosis Neuronal 8 AR 600143
Ceroid Lipofuscinosis Neuronal 8, Northern Epilepsy Variant AR 610003
Cognitive Impairment With Or Without Cerebellar Ataxia AD 614306
Combined oxidative phosphorylation deficiency 14 AR 614946
Congenital Disorder of Deglycosylation AR 615273
Congenital Disorder of Glycosylation Type IIm XL 300896
Convulsions, Familial Infantile, with Paroxysmal Choreoathetosis AD 602066
Cornelia de Lange syndrome 2 XL 300590
Cortical Dysplasia-Focal Epilepsy Syndrome AR 610042
Deficiency Of Guanidinoacetate Methyltransferase AR 612736
Developmental and Epileptic Encephalopathy 4 AD 612164
Dystonia 9 AD 601042
Encephalopathy, Neonatal Severe, Due To Mecp2 Mutations XL 300673
Epilepsy, Childhood Absence 2 AD 607681
Epilepsy, Childhood Absence 5 612269
Epilepsy, familial focal, with variable foci AD 604364
Epilepsy, Familial Focal, with Variable Foci 3 AD 617118
Epilepsy, familial focal, with variable foci 4 AD 617935
Epilepsy, focal, with speech disorder and with or without mental retardation AD 245570
Epilepsy, Hearing Loss, and Mental Retardation Syndrome AR 616577
Epilepsy, idiopathic generalized, susceptibility to, 14 AD 616685
Epilepsy, Idiopathic Generalized, Suscpetibility to, 12 AD 614847
Epilepsy, Juvenile Myoclonic 5 611136
Epilepsy, nocturnal frontal lobe, 5 AD 615005
Epilepsy, Progressive Myoclonic 3 AR 611726
Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp AR 608105
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, 19 AD 615744
Epileptic Encephalopathy, Early Infantile, 2 XL 300672
Epileptic Encephalopathy, Early Infantile, 23 AR 615859
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, 27 AD 616139
Epileptic Encephalopathy, Early Infantile, 28 AR 616211
Epileptic Encephalopathy, Early Infantile, 3 AR 609304
Epileptic Encephalopathy, Early Infantile, 31 AD 616346
Epileptic Encephalopathy, Early Infantile, 32 AD 616366
Epileptic Encephalopathy, Early Infantile, 33 AD 616409
Epileptic Encephalopathy, Early Infantile, 34 AR 616645
Epileptic Encephalopathy, Early Infantile, 35 AR 616647
Epileptic Encephalopathy, Early Infantile, 36 XL 300884
Epileptic Encephalopathy, Early Infantile, 37 AR 616981
Epileptic Encephalopathy, Early Infantile, 39 AR 612949
Epileptic Encephalopathy, Early Infantile, 41 AD 617105
Epileptic Encephalopathy, Early Infantile, 42 AD 617106
Epileptic Encephalopathy, Early Infantile, 43 AD 617113
Epileptic Encephalopathy, Early Infantile, 44 AR 617132
Epileptic Encephalopathy, Early Infantile, 45 AD 617153
Epileptic Encephalopathy, Early Infantile, 46 AD 617162
Epileptic Encephalopathy, Early Infantile, 47 AD 617166
Epileptic Encephalopathy, Early Infantile, 48 AR 617276
Epileptic Encephalopathy, Early Infantile, 49 AR 617281
Epileptic Encephalopathy, Early Infantile, 5 AD 613477
Epileptic Encephalopathy, Early Infantile, 51 AR 617339
Epileptic encephalopathy, early infantile, 52 AR 617350
Epileptic Encephalopathy, Early Infantile, 53 AR 617389
Epileptic Encephalopathy, Early Infantile, 54 AD 617391
Epileptic Encephalopathy, Early Infantile, 55 AR 617599
Epileptic Encephalopathy, Early Infantile, 56 AD 617665
Epileptic encephalopathy, early infantile, 57 AD 617771
Epileptic Encephalopathy, Early Infantile, 58 AD 617830
Epileptic Encephalopathy, Early Infantile, 59 AD 617904
Epileptic encephalopathy, early infantile, 60 AR 617929
Epileptic Encephalopathy, Early Infantile, 62 AD 617938
Epileptic encephalopathy, early infantile, 63 AR 617976
Epileptic encephalopathy, early infantile, 64 AD 618004
Epileptic encephalopathy, early infantile, 65 AD 618008
Epileptic encephalopathy, early infantile, 66 AD 618067
Epileptic encephalopathy, early infantile, 67 AD 618141
Epileptic Encephalopathy, Early Infantile, 7 AD 613720
Epileptic encephalopathy, early infantile, 70 AD 618298
Epileptic encephalopathy, early infantile, 71 AR 618328
Epileptic encephalopathy, early infantile, 74 AD 618396
Epileptic Encephalopathy, Early Infantile, 8 XL 300607
Epileptic encephalopathy, early infantile, 85, with or without midline brain defects 301044
Epileptic Encephalopathy, Early Infantile, 9 XL 300088
Epileptic Encephalopathy, Infantile or Early Childhood, 2 AD 617829
Episodic Ataxia Type 2 AD 108500
Episodic Kinesigenic Dyskinesia 1 AD 128200
Esophageal Cancer 133239
Familial Hemiplegic Migraine Type 1 AD 141500
Generalized Epilepsy And Paroxysmal Dyskinesia AD 609446
Generalized Epilepsy With Febrile Seizures Plus, Type 1 AD 604233
Generalized epilepsy with febrile seizures plus, type 10 AD 618482
Generalized Epilepsy With Febrile Seizures Plus, Type 2 AD 604403
Generalized Epilepsy With Febrile Seizures Plus, Type 7 AD 613863
Generalized Epilepsy with Febrile Seizures Plus, Type 9 AD 616172
Global developmental delay, progressive ataxia, and elevated glutamine AR 618412
Glut1 Deficiency Syndrome 1 AD 606777
Glut1 Deficiency Syndrome 2 AD 612126
Hyperphosphatasia With Mental Retardation AR 239300
Hyperphosphatasia with mental retardation syndrome 2 AR 614749
Indifference To Pain, Congenital, Autosomal Recessive AR 243000
Kohlschutter-Tonz syndrome AR 226750
Liang-Wang syndrome AD 618729
Lymphangioleiomyomatosis 606690
MECP2 Duplication Syndrome XL 300260
Mental Retardation, Autosomal Dominant 1 AD 156200
Mental Retardation, Autosomal Dominant 31 AD 616158
Mental retardation, autosomal dominant 38 AD 616393
Mental Retardation, Autosomal Dominant 5 AD 612621
Mental Retardation, Autosomal Dominant 6 AD 613970
Mental Retardation, Autosomal Dominant 8 AD 614254
Mental Retardation, Autosomal Recessive 12 AR 611090
Mental Retardation, Stereotypic Movements, Epilepsy, And/Or Cerebral Malformations AD 613443
Mental Retardation, X-linked 49 XL 300114
Mental Retardation, X-Linked, Syndromic 13 XL 300055
Mental Retardation, X-Linked, Syndromic, Christianson Type XL 300243
Mental Retardation, X-Linked, With Or Without Seizures, Arx-Related XL 300419
Mitochondrial DNA Depletion Syndrome 4B, Mngie Type AR 613662
Molybdenum Cofactor Deficiency C AR 615501
Mowat-Wilson Syndrome AD 235730
Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 XL 300868
Myoclonic Epilepsy, Familial Infantile AR 605021
Myoclonic-Atonic Epilepsy AD 616421
Nephrotic Syndrome, Type 15 AR 617609
Neurodegeneration With Brain Iron Accumulation 5 XL 300894
Neurodevelopmental disorder with cerebellar atrophy and with or without seizures AR 618056
Neurodevelopmental Disorder with Involuntary Movements AD 617493
Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive AR 617820
Neurodevelopmental disorder with poor language and loss of hand skills AD 617903
Paroxysmal Extreme Pain Disorder AD 167400
Paroxysmal Nocturnal Hemoglobinuria 300818
Partington X-Linked Mental Retardation Syndrome XL 309510
Pitt-Hopkins-like syndrome 2 AR 614325
Primary Erythromelalgia AD 133020
Progressive Sclerosing Poliodystrophy AR 203700
Proud Levine Carpenter Syndrome XL 300004
Pyridoxal 5'-Phosphate-Dependent Epilepsy AR 610090
Pyridoxine-Dependent Epilepsy AR 266100
Rett Syndrome XL 312750
Rett Syndrome, Congenital Variant AD 613454
Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal AR 614498
Seizures, Benign Familial Infantile, 2 AD 605751
Seizures, benign familial infantile, 5 AD 617080
Seizures, Benign Familial Neonatal, 2 AD 121201
SeSAME Syndrome AR 612780
Spastic Paraplegia 77 AR 617046
Spinocerebellar Ataxia 6 AD 183086
Spinocerebellar ataxia, autosomal recessive 12 AR 614322
Spinocerebellar ataxia, autosomal recessive 7 AR 609270
Stomatin-deficient cryohydrocytosis with neurologic defects AD 608885
Tuberous Sclerosis 1 AD 191100
Tuberous Sclerosis 2 AD 613254
{Epilepsy, idiopathic generalized, susceptibility to, 16} AD 618596

Related Test



  • 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
  • Chou et al. 2014. PubMed ID: 25520928
  • Della Mina et al. 2015. PubMed ID: 24848745
  • Dilena et al 2016. PubMed ID: 26212315
  • Human Gene Mutation Database (Bio-base).
  • Hynynen et al. 2014. PubMed ID: 25065347
  • Khan and Al Baradie. 2012. PubMed ID: 23213494
  • Kodera et al. 2013. PubMed ID: 23662938
  • Kullmann. 2002. PubMed ID: 12023309
  • 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
  • Musto et al. 2020. PubMed ID: 31889633
  • Myers and Scheffer 2017 PubMed ID: 28406046
  • Noh et al. 2012. PubMed ID: 22342633
  • Ottman et al. 2010. PubMed ID: 20100225
  • Palavra et al 2017. PubMed ID: 28386314
  • Pierson et al 2014. PubMed ID: 24839611
  • Ream and Mikati. 2014. PubMed ID: 25108116
  • Reif et al. 2017. PubMed ID: 27781560
  • 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


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