BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for Epilepsy

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018

DESCRIPTION

Epilepsy is a heterogeneous condition that encompasses many types of seizures that vary in age of onset and severity. Classification is typically based on seizure type (e.g., simple partial, complex partial, generalized, convulsive, non-convulsive) or age of onset (i.e., neonatal, infancy, childhood, adolescent/adult).

The intent of this medical policy is to address genetic testing for epilepsy syndromes that present in infancy or early childhood, are severe, and are characterized by seizures as the primary manifestation without associated metabolic or structural brain abnormalities. Mutations in many genes have been associated with early onset epilepsies. Specific clinical syndromes and their associated genes are demonstrated in the following table:

Single-Gene Mutations Associated with Epileptic Syndromes

Syndrome

Associated Genes

Dravet syndrome (presents between 4 and 15 months with prolonged convulsive seizures; severe developmental delay also known as myoclonic epilepsy in infancy [SMEI] or polymorphic myoclonic epilepsy in infancy [PMEI])

SCN1A, SCN9A, GABRA1, STXBP1, PCDH19, SCN1B, CHD2, HCN1

Early infantile epileptic encephalopathy with suppression burst (Ohtahara syndrome)

 KCNQ2, SLC25A22, STXBP1, CDKL5, ARX

EFMR syndrome (epilepsy limited to females with mental retardation)

PCDH19

Nocturnal frontal lobe epilepsy (epileptic encephalopathy with continuous spike-and-wave during sleep)

GRIN2A

GEFS+ syndrome (genetic epilepsies with febrile seizures plus)

SCN1A, SCN9A

Landau-Kleffner syndrome (aphasia with convulsions)

GRIN2A

West syndrome (the most common with onset within the first 2 years; hypsarrhythmia on interictal EEG, and developmental delay; also known as X-linked infantile spasm syndrome)

ARX, TSC1, TSC2, CDKL5, ALG13, MAGI2, STXBP1, SCN1A, SCN2A, GABA, GABRB3, DNM1

Glucose transporter type 1 deficiency syndrome

SLC2A1

Another area of interest for epilepsy research is the pharmacogenomics of anti-epileptic medications used to treat these syndromes. It has been proposed that by identifying genetic markers in individuals who are likely to be refractory to common medications, a more efficient process for medication selection and more effective control of symptoms could be developed.

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION  

The common epilepsy syndromes, also known as idiopathic epilepsy, generally present in childhood, adolescence, or early adulthood. They include generalized or focal in nature and may be convulsant (grand mal) or absence type. There is a lack of evidence on the clinical utility of genetic testing for the common genetic epilepsies.

SOURCES

Allen, N., Conroy, J., Shahwan, A., Lynch, B., Correa, R., Pena, S., et al. (2016). Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion. Epilepsia, 57 (1), e12-e1. (Level 3 evidence)

Balciuniene, J., DeChene, E.T., Akgumus, G., Romasko, E.J., Cao, K., Dubbs, H.A., & et al. (2019). Use of a dynamic genetic testing approach for childhood-onset epilepsy. JAMA Network Open, 2 (4), e192129. (Level 4 evidence)

BlueCross BlueShield Association. Evidence Positioning System. (3:2021). Genetic testing for epilepsy (2.04.109). Retrieved July 7, 2021 from https://www.evidencepositioningsystem.com/. (80 articles and/or guidelines reviewed)

Hrabik, S.A., Standridge, S.M., Greiner, H.M., Neilson, D.E., Pilipenko, V.V., Zimmerman, S.L., et al. (2015). The clinical utility of a single-nucleotide polymorphism microarray in patients with epilepsy at a tertiary medical center. Journal of Child Neurology, 30 (13), 1770-1777. (Level 4 evidence)

International League against Epilepsy (ILAE). (2015). Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia, 56 (8), 1185-1197.

Lindy, A.S., Butler, E., Pickersgill, C, D., Shanmugham, A., Retterer, K., Brandt, T., et al. (2018). Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopment disorders. Epilepsia, 59 (5). (Level 4 evidence)  

Mercimek-Mahmutoglu, S., Patel, J., Cordeiro, D., Hewson, S., Callen, D., Donner, E., et al. (2015). Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epelepsia, 56 (5), 707-716. (Level 3 evidence)

Wirrell, E. C., Shellhaas, R. A., Joshi, C., Keator, C., Kumar, S., Mitchell, W.G., et al. (2015). How should children with West syndrome be efficiently and accurately investigated?  Results from the National Infantile Spasms Consortium. Epilepsia, 56 (4), 617-625. (Level 3 evidence)

ORIGINAL EFFECTIVE DATE:  6/14/2014

MOST RECENT REVIEW DATE:  8/12/2021

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