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Patient/Member Information

Patient Name: DOB:

Payor: Plan:

Subscriber Name:DOBSubscriber Number:

Provider/Contact Information

Ordering Provider:

Contact Person:Phone:Fax:

Genetic Test Information

Name of test: Epilepsy Panel (89 genes)

Test Code:03402

CPT code(s):81479

ICD10 code(s):

List price:

Do you have a preferred clinical laboratory for genetic testing?

__ NO(or not applicable)

X YES, (provide preferred lab name): Invitae

Please state the reason why testing should/must be performed at this laboratory:

Clinical Reasoning for Genetic Test (Attach the clinic note)

*** is a ***yowith a history of ***.

-What laboratory and/or clinical testing have been performed to date (genetic and other testing)?

-Why is genetic testing necessary at this time?Epilepsy is a group of disorders caused by disturbances with electrical signaling in the brain. Epilepsy may present as an isolated finding or as part of a broader phenotype. Several syndromic neurodevelopmental disorders include epilepsy as a prominent feature. Furthermore, several phenotypic subgroups of epilepsy exist. 1 These types include early-onset spasms, X-linked infantile spasms, Dravet and related syndromes, Ohtahara syndrome, epilepsy and mental retardation limited to females (now known as PCDH19 female-limited epilepsy), early-onset absence epilepsy, autosomal dominant nocturnal frontal lobe epilepsy, and epilepsy with paroxysmal exercise-induced dyskinesia. Distinction between the phenotypic subgroups provides helpful information for prognostic and genetic counseling and clinical care.

Epilepsy is a highly heterogeneous genetic disorder, meaning many genes have been associated with epilepsy. For example, mutations in genes encoding ion channels, proteins associated to the vesical synaptic cycle or proteins involved in energy metabolism are known to cause epilepsy. The large number of genes associated with epilepsy complicates the genetic diagnosis.

-How will the results of the genetic test, whether negative or positive, impact the future management of the member being tested? (explainall that apply):

Stop the need for further diagnostic testing:As the NGS assay covers multiple relevant genes using a single blood draw, it can potentially help avoid a long series of laborious, costly, and stressful diagnostic procedures.

Inform on prognosis:

Change treatment plan (e.g. medical or surgical decision-making or treatment):Depending on the specific mutations identified, test results could help guide antiepileptic pharmacotherapy in some cases. For example, administration of sodium channel blockers would be avoided in patients with Dravet syndrome harboring an SCN1A mutation, while detection of an ALDH7A1 mutation might suggest responsiveness to pyridoxine (depending on other clinical features).7

Change surveillance (e.g. annual echocardiograms, either begin or stop):The following surveillance may be required:EEG, neuropsychological evaluation, hearing evaluation, developmental assessment, speech/language evaluation,

Provide information for family members:Inherited epilepsy disorders can occur in several inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked dominant. Identification of a causal mutation will allow for accurate recurrence risk counseling.

-What is the probability that this test will be positive? If this is not known, then please indicate which clinical features increase the probability that this test will provide a diagnosis. The large number of genes with putative links to epilepsy complicates the identification of an underlying genetic. Next-generation sequencing (NGS) allows sequencing of numerous genes simultaneously. NGS panels are appropriate and more cost effective for detecting mutations in disorders with a highly heterogeneous genetic background, such as epilepsy.4

-If this is a request is for a gene panel, then please describe why a single gene test is not as useful.The clinical sensitivity of this test is dependent on the patient’s underlying genetic condition. For each condition, the table below shows the percentage of clinical cases in which a pathogenic variant is expected to be identified through analysis of the genes on this panel.

Sensitivity by clinical condition / Genes
71% of epileptic encephalopathy / CHD2, CDKL5, KCNQ2, PCDH19, SCN1A, SCN2A, SYNGAP1
90% of benign familial epilepsy ( / KCNQ2, KCNQ3, PRRT2, SCN2A
75% of Dravet syndrome / PCDH19, SCN1A
35% of Ohtahara syndrome / STXBP1
20%–25% of autosomal dominant nocturnal frontal lobe epilepsy / CHRNA2, CHRNA4, CHRNB2, DEPDC5, KCNT1
10% of early onset absence epilepsy and 90% of GLUT1 deficiency encephalopathy / SLC2A1
Unknown for rare subtypes of EIEE / ADSL, ALDH7A1, ALG13, ARHGEF9, ARX, ATP1A2, CACNA2D2, CLN3, CLN5, CLN6, CLN8, CSTB, CTSD, DNAJC5, EFHC1, EPM2A, FOLR1, GABRA1, GABRB3, GABRG2, GAMT, GATM, GNAO1, GOSR2, GRIN1, GRIN2A, GRIN2B, HCN1, HNRNPU, KCNH2, KCNJ10, KCTD7, LGI1, LIAS, MFSD8, NHLRC1, PLCB1, PNKP, PNPO, POLG, PPT1, PRICKLE1, QARS, RBFOX1, ROGDI, SCARB2, SCN1B, SCN3A, SCN5A, SCN9A, SLC25A22, SLC35A2, SLC6A8, SPTAN1, SYN1, TBC1D24, TPP1, TSC1, TSC2, WWOX
Rett/Atypical Rett syndromes / MECP2: 95% of females with Rett syndrome cases and 75% of females with atypical Rett syndrome cases; CDKL5: 13% of atypical Rett syndrome cases; FOXG1: 1% of Rett syndrome cases; MBD5 and MEF2C are rare causes of Rett-like syndrome.
Angelman/Angelman-like syndromes* / UBE3A: 90% of Angelman syndrome cases; SLC9A6: 6% of Angelman syndrome cases; MBD5: Rare cause of Angelman-like syndrome (Christianson syndrome) cases); MECP2: Rare cause of Angelman-like syndrome cases.
Pitt-Hopkins syndrome / TCF4: 38% of Pitt-Hopkins syndrome cases.
Mowat-Wilson syndrome** / ZEB2: 98% of Mowat-Wilson syndrome cases.
Koolen-DeVries syndrome (17q21.31 microdeletion syndrome) / KANSL1: 100% of Koolen-DeVries syndrome cases.
adenylosuccinatelyase deficiency / ADSL: 100% of adenylosuccinatelyase deficiency cases
alpha-thalassemia X-linked intellectual disability (ATRX) syndrome / ATRX: 100% of ATRX syndrome cases.
Glass syndrome / SATB2: 100% of Glass syndrome
succinic semialdehyde dehydrogenase (SSADH) deficiency / ALDH5A1: 100% of SSADH deficiency cases.