Genetic testing performed to diagnose patients with signs and symptoms of possible genetic disease is generally covered.  In addition, the test results must have a direct effect on the patient's treatment.

Genetic testing performed on patients with no current evidence or manifestation of genetic disease (i.e., asymptomatic) is considered genetic screening and is non-covered except for those groups/programs that specifically identify coverage in benefits. This includes genetic testing performed to determine susceptibility or predisposition to diseases such as cancer and heart disease and genetic testing for carrier identification to determine if a person is a "carrier" of an abnormal gene.

The following testing is covered for symptomatic patients. The testing is also covered for asymptomatic patients when the patient's contract covers genetic screening. This is not an all-inclusive list.

• Inherited BRCA-1 or BRCA-2 mutations for breast and ovarian cancer (S3818, S3819, S3820, S3822, S3823)
• Germline mutations of the RET proto-oncogene in medullary carcinoma of the thyroid
• Inherited susceptibility to colon cancer (S3828, S3829, S3830, S3831, S3833, S3834)
• Cystic fibrosis (S3835)
• Hemochromatosis (S3837)
• Retinoblastoma (S3841)
• Von Hippel-Lindau disease (S3842)
• Alpha-thalassemia (S3845)
• E beta thalassemia (S3846)
• Tay-Sachs disease (S3847)
• Gaucher disease (S3848)
• Niemann-Pic diseases (S3849)
• Sickle cell anemia (S3850)
• Canavan disease (S3851)
• Multiple endocrine neoplasia type 2 (S3840)
• Factor V Leiden thrombophilia (S3843)
• Congenital profound deafness (S3844)
• Myotonic muscular dystrophy (S3853)
• Hypertrophic cardiomyopathy (S3865, S3866)
• Fragile X syndrome (FXS)

Genetic Testing for Diagnosis or Risk Assessment of Alzheimer's Disease
Genetic testing for diagnosis or risk assessment of Alzheimer's disease (S3852, S3855) is considered experimental/investigational and not eligible for payment. This includes, but is not limited to, testing for the apolipoprotein E epsilon 4 allele, presenilin genes, or amyloid precursor gene. There is no evidence that testing for genetic mutations improves the sensitivity or specificity of clinical criteria and would not alter diagnostic testing for other causes of dementia. A participating, preferred, or network provider can bill the member for the denied service.

Date Last Reviewed: 08/2010

Genetic Testing for Mutations Associated with Malignant Melanoma Susceptibility
Genetic testing for mutations associated with susceptibility to malignant melanoma (89240) is considered experimental/investigational and not eligible for payment. A participating, preferred, or network provider can bill the member for the denied test. A genetic predisposition to malignant melanoma is suspected when melanoma has been diagnosed in multiple family members, when multiple primary melanomas are identified in a single patient, and when there is an early age of onset. While some of the familial risk may be related to shared environmental factors, two main genes (CDKN2A and CDK4) involved in melanoma susceptibility have been identified. The incidence of CDKN2A mutations in the general population is very low. However, the incidence of CDKN2A mutations increases with a positive family history, rising to 20-40% in kindreds with 3 or more affected first degree relatives. CDK4 has been identified in only three families worldwide. Currently, management of patients considered at high risk for malignant melanoma focuses on reduction of sun exposure, use of sun screens, vigilant cutaneous surveillance of pigmented lesions, and prompt biopsy of suspicious lesions. The published data on genetic testing of the CDKN2A gene focus on the underlying genetics of hereditary melanoma, identification of mutations in families at high risk of melanoma, and risk in those harboring CDKN2A mutations. However, there is a lack of published studies that focus on how genetic testing of the CDKN2A gene would result in improvement in patient management.

Date Last Reviewed: 03/2010

Genetic Testing for Long QT Syndrome
Genetic testing (e.g., the Familion® test) (S3860, S3861, S3862 ) is covered in patients with suspected congenital long QT syndrome who meet the following clinical criteria:

• QT measurement that is greater than or equal to 460 msec, or
• a history of torsades de pointes, or
• the presence of both T-wave alternans and notched T waves in three leads.

Genetic testing is also covered in individuals who do not meet the clinical criteria for LQTS, but who have:

• a close relative (i.e., first-, second-, or third-degree relative) with a known LQTS mutation; or
• a close relative diagnosed with LQTS by clinical means whose genetic status is unavailable.

Genetic testing for LQTS to determine prognosis and/or to direct therapy in individuals with known LQTS is considered investigational. A participating, preferred, or network provider can bill the member for the denied test in this case.

Long QT syndrome (LQTS) is an inherited disorder of the heart’s electrical system characterized by prolongation of the QT interval. LQTS is a defect in the ion channel which causes a delay in the time it takes for the electrical system to recharge after each heartbeat. LQTS predisposes the individual to cardiac events such as torsades de pointes, which may in turn result in syncope and sudden cardiac death. LQTS may also be caused by acquired factors, most commonly by use of certain drugs that will cause prolongation of the QT interval. Management has focused on the use of beta blockers as first-line treatment, with pacemakers or implantable cardiac defibrillators (ICD) as second-line therapy.

Diagnosis criteria for LQTS have been established which focus on EKG findings and clinical and family history (e.g., the Schwartz criteria and Keatings criteria). However, measurement of the QT interval is not well standardized, and in some cases, patients may be considered borderline cases. 

LQTS has recently been characterized as an “ion channel disease,” with abnormalities in the sodium and potassium channels that control the excitability of the cardiac myocytes. A genetic basis for LQTS has also emerged, with 7 different variants recognized, each corresponding to mutation in different genes. In addition, typical ST-T-wave patterns are also suggestive of specific subtypes. There are several forms of LQTS, depending on the genes responsible and the features associated with the condition. Most forms of LQTS are carried in an autosomal dominant manner. Terminology LQT1, LQT2, LQT3, LQT 4-7 refer to the locus name of the genes involved, or the phenotype.

Date Last Reviewed:  11/2010

Genetic Testing for Developmental Delay, Autism Spectrum Disorder and/or Mental Retardation
Comparative genomic hybridization (CGH) microarray testing for developmental delay, autism spectrum disorder and/or mental retardation (S3870) is considered experimental/investigational and not eligible for payment. There is insufficient evidence in the scientific research to support any positive affect on clinical outcomes. A participating, preferred, or network provider can bill the member for the denied test.

Date Last Reviewed: 03/2009

Genetic testing is a complex process. The results depend on reliable laboratory procedures and accurate interpretation of results. When no code exists, molecular diagnostic testing (codes 83890-83914, 88384-88386) and cytogenetic testing (codes 88230-88291) may be reported for genetic testing. Different combinations of the codes may be reported depending on the clinical circumstances. In some cases, certain codes may be reported multiple times.

Genetic counseling (S0265, 96040) is generally provided in conjunction with genetic testing. Counseling usually occurs when the results of the tests are provided to the patient and intervention strategies are discussed. Coverage for genetic counseling is determined according to individual or group customer benefits. When genetic testing is non-covered, the counseling performed in conjunction with the testing is also non-covered.

NOTE:

See Medical Policy Bulletins U-4 and U-6 for information on prenatal genetic testing.

Description

Genetic diseases are conditions resulting in abnormalities of DNA. Some genetic diseases are transmitted from parents to their children, and in other circumstances, genetic diseases may occur spontaneously, as in mutations.

NOTE:

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

This medical policy may not apply to FEP. Medical policy is not an authorization, certification, explanation of benefits or a contract. Benefits are determined by the Federal Employee Program.

National Blue Cross Blue Shield Association Medical Policy 2.04.02, Genetic Testing for Inherited BRCA1 or BRCA2 Mutations, 03/2002

National Blue Cross Blue Shield Association Medical Policy 2.04.05, Genetic Testing for Germline Mutations of the RET Proto-Oncogene in Medullary Carcinoma of the Thyroid, 11/1998

National Blue Cross Blue Shield Association Medical Policy 2.04.08, Genetic Testing for Inherited Susceptibility to Colon Cancer Including Microsatellite Instability, 03/2002

National Blue Cross Blue Shield Association Medical Policy 2.04.13, Genetic Testing for Familial Alzheimer's Disease, 1:2006

National Blue Cross Blue Shield Association Medical Policy 2.04.44, Genetic Testing for Mutations Associated with Malignant Melanoma Susceptibility, 8:2008

Limited Family Structure and BRCA Gene Mutation Status in Single Cases of Breast Cancer, JAMA, Volume 297, No. 23, 6/2007

CKN2A Germline Mutations in Individuals with Cutaneous Malignant Melanoma, J Invest Dermatol, Volume 127, No.5, 5/2007

Cutaneous Phenotype and MC1R Variants as Modifying Factors for the Development of Melanoma in CDKN2A G101W Mutation Carriers From 4 Countries, Int J Cancer, Volume 121, No. 4, 08/2007

Features Associated with Germline CDKN2A Mutations: a GenoMEL Study of Melanoma-Prone Families From Three Continents, J Med Genet, Volume 44, No. 2, 02/2007

Genodermatoses With Cutaneous Tumors and Internal Malignancies, Dermatol Clin, Volume 26, No. 1, 01/2008

RTI International of North Carolina Evidence Based Practice Center, HSTAT. Guide to Clinical Preventive Services. 3rd ed.  Available at www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat3.section.28281.  Accessed June 8, 2008

Chao S, Roberts JS, Marteau TM, Silliman R, Cupples LA, Green RC. Health Behavior Changes After Genetic Risk Assessment for Alzheimer Disease: The REVEAL Study. Alzheimer Dis Assoc Disord. 2008;22(1):94-97

Lane R, Feldman HH, Meyer J, et al. Synergistic effect of apolipoprotein E є4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer’s disease. Pharmacogenetics and Genomics. 2008;18(4): 289-297

Bird TD. Alzheimer Disease Overview. GeneReviews. Revised June 13, 2007.  Available at www.genetests.org/servlet/access?id=8888892&key=dEBZcf8MDbEwx&gry=INS.  Accessed April 22, 2008

Zappasodi F, Salustri C. Claudia B. et al. An observational study on the influence of the APOE- є4 allele on the correlation between ‘free’ copper toxicosis and EEG activity in Alzheimer disease. Brain Research. 2008. Available at www.sciencedirect.com

Coon KD, Myers AJ, Craig DW, et al. A High-Density Whole-Genome Association Study Reveals That APOE Is the Major Susceptibility Gene for Sporadic Late-Onset Alzheimer’s Disease. J Clin Psychiatry. 2007;68(4):613-618

National Blue Cross Blue Shield Association Medical Policy 2.04.43, Genetic Testing for Congenital Long QT Syndrome, 07: 2010

2007 BCBS TEC Assessment, Genetic Testing for Long QT Syndrome. 2008;22(9)

Hofman N, Wilde AM, Kaab S, et al. Diagnostic Criteria for Congenital Long QT Syndrome in the Era of Molecular Genetics: Do we need a Scoring System. European Heart Journal. 2007;28:575-580

Schwartz PJ, Moss AJ, Vincent, et al. Diagnostic Criteria for the Long QT Syndrome: An Update. Circulation. 1993;88(2):782-784

Aspinwall LG, Leaf SL, Dola ER, et al. CDKN2A/p 16 genetic test reporting improves early detection intentions and practices in high-risk melanoma families.  Cancer Epidemiol Biomarkers Prev 2008; 17(6):1510-9.

Ibrahim N, Haluska FG. Molecular patholgenesis of cutaneous melanocytic neoplasms. Annu Rev Pathol. 2009; 4:551-9.

Council ML, Gardner JM, et al. Contribution of genetic factors of melanoma susceptibility in sporadic US melanoma patients. Exp Dermatol. 2009 May; 18(5):485-7.

Nelson AA, Tsao H. Melanoma and genetics. Clin Dermatol. 2009 Jan-Feb;27(1):46-52.

3rd Canadian Consensus Conference on Diagnosis and Treatment of Dementia. Third Canadian Consensus Conference on Diagnosis and Treatment of Dementia. July 2007

Statement on Use of Apolipoprotein E  Testing for Alzheimer Disease. Bethesda, MD. American College of Medical Genetics. May 23, 2007

Waldemar G, Dubois B, Emre M. Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol. January 2007;14(1): e1-26

Patterson C, Feightner J, Garcia A, et. al. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. Canadian Medical Association Journal. February 2008;178(5) www.mdconsult.com

Seashore M. Genetic Risk Assessment. In: Goldman: Cecil Medicine, 23rd ed. Saunders;2007. www.mdconsult.com

Schipper H. Apolipoprotein E: Implication for AD neurobiology, epidemiology and risk assessment. Neurobiology of Aging. May 29, 2009/ epub

Green R, Roberts J, Cupples L, et. al. Disclosure of APOE Genotype for Risk of Alzheimer’s Disease. NEJM. July 2009;361: 245-54

The National Guidelines Clearinghouse. Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. www.guideline.gov

Bertram L, Tanzi R. Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci. October 2008;9(10): 768 – 78

The American Academy of Neurology. Practice parameter: Diagnosis of dementia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001:56: 1143 – 1153

Anderson H. Alzheimer Disease. May 6, 2010  www.emedcine.medscape.com/article/1134817

Sze E, Moss AJ, Goldenberg I, et al. Long QT syndrome in patients over 40 years of age: increased risk for LQTS-related cardiac events in patients with coronary disease. Ann Noninvasive Electrocardiol. 2008;13(4):327-331.

Kapa S, Tester DJ, Salisbury BA, et al. Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009;120(18):1752-1760.

Jons C, Moss AJ, Lopes CM, et al. Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long-QT syndrome. J Cardiovasc Electrophysiol. 2009;20(8):859-865.

Kapplinger JD, Tester DJ, Salisbury BA, CarrJL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ. Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009;6(9):1297-1303.