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.

• Germline mutations of the RET proto-oncogene in medullary carcinoma of the thyroid
• Inherited susceptibility to colon cancer (81292, 81293, 81294, 81295, 81296, 81297, 81298, 81299, 81300, 81301, 81317, 81318, 81319, S3833, S3834)
• Cystic fibrosis (81220, 81221, 81222, 81223, 81224)
• Hemochromatosis (81256)
• Retinoblastoma (S3841)
• Von Hippel-Lindau disease (S3842)
• Alpha-thalassemia (81257, S3845)
• E beta thalassemia (S3846)
• Tay-Sachs disease (81255)
• Gaucher disease (81251)
• Niemann-Pic diseases (81330, S3849)
• Sickle cell anemia (S3850)
• Canavan disease (81200)
• Multiple endocrine neoplasia type 2 (S3840)
• Factor V Leiden thrombophilia (81241)
• Congenital profound deafness (S3844)
• Myotonic muscular dystrophy (S3853)
• Hypertrophic cardiomyopathy (S3865, S3866)
• Fragile X syndrome (FXS) (81243, 81244)

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) (81280, 81281, 81282, S3861) 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.
• The individual has signs and/or symptoms indicating a moderate-to-high pretest probability of LQTS using the Schwartz criteria

Schwartz et al Diagnostic Criteria for Long QT Syndrome TABLE 1. 1985 LQTS Diagnostic Criteria

The diagnosis of Long QT Syndrome is made in the presence of either two major criteria or of one major and two minor criteria.

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: 05/2012

Genetic Testing for Brugada (S3861)
Genetic testing for Brugada (S3861) is covered for patients who meet the following criteria for Class I of the Heart Rhythm Society and the European Heart Rhythm Association recommendations:

• Mutation-specific genetic testing is covered for family members and appropriate relatives following the identification of the BrS-causative mutation in an index case.

The following Class II indication will only be covered on a case by case basis:

• Comprehensive or BrSI targeted BrS genetic testing for any patient in whom a cardiologist has established a clinical index of suspicion for BrS based on examination of the patient’s clinical history, family history and expressed electrocardiographic (resting 12-lead ECGs and/or provocative drug challenge resting) phenotype. 

Brugada syndrome is an inherited condition comprising a specific EKG abnormality and an associated risk of ventricular fibrillation and sudden death in the setting of a structurally normal heart. It is characterized by ST-segment abnormalities on EKG and a high risk of ventricular arrhythmias and sudden death.  Brugada syndrome presents primarily during adulthood but age at diagnosis ranges from 2 days to 85 years.  Clinical presentations may also include sudden infant death syndrome and sudden unexpected nocturnal death syndrome, a typical presentation in individuals from Southeast Asia.

Date Last Reviewed: 05/2012

Genetic Testing for Catecholaminergic Polymorphic Ventricular Tachycardia (CVPT)
Genetic testing for CVPT is covered for patients who meet the following criteria for Class I of the Heart Rhythm Society and the European Heart Rhythm Association recommendations:

• Comprehensive or CPVT1 and CPVT 2 targeted CPVT genetic testing for any patient in whom a cardiologist has established a clinical index of suspicion for CPVT based on examination of the patient’s clinical history, family history, and expressed electrocardiographic phenotype during provocative stress testing with cycle, treadmill, or catecholamine infusion.
  
  
• Mutation-specific genetic testing for family members and appropriate relatives following the identification of the CPVT-causative mutation in an index case.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly lethal form of inherited arrhythmogenic disease characterized by adrenergically mediated polymorphic ventricular tachycardia.  Mutations in the cardiac ryanodine receptor (RyR2) gene and the cardiac calsequestrin (CASQ2) gene are responsible for the autosomal dominant and recessive variants of CPVT, respectively.  The clinical presentation encompasses exercise- or emotion-induced syncopal events and a distinctive pattern of reproducible, stress-related, bi-directional ventricular tachycardia in the absence of both structural heart disease and a prolonged QT interval.

CPVT typically begins in childhood or adolescence. The mortality rate in untreated individuals is 30 to 50% by age 40 years.  Clinical evaluation by exercise stress testing and Holter monitoring and genetic screening can facilitate early diagnosis.  Beta-blockers are the most effective drugs for controlling arrhythmias in CPVT patients, yet about 30% of patients with CPVT still experience cardiac arrhythmias on beta-blockers and eventually require an implantable cardioverter defibrillator.

Although the clinical presentation of CPVT is similar in many respects to the LQTS, there are important differences that are relevant to genetic testing. CPVT appears to be a more malignant condition, as many people are asymptomatic before the index lethal event and the majority of cardiac events occur before 20 years of age. Affected people are advised to avoid exercise-related triggers and start prophylactic beta-blockers with dose titration guided by treadmill testing.

Genetic testing has been recommended in individuals with clinical features considered typical of CPVT following expert clinical assessment. Clinically the condition is difficult to diagnose in asymptomatic family members as the ECG and echocardiogram are completely normal at rest. Exercise stress testing has been advised in family members in order to identify exercise-induced ventricular arrhythmias, but the sensitivity of this clinical test is unknown. Although the diagnostic yield from genetic testing is less than that for the LQTS (about 50%) in patients with typical clinical features, a positive genetic test may be of value for the individual patient (given the prognostic implications) and for screening family members (given the difficulties in clinical screening methods). The RyR2 gene is large and a ‘‘targeted’’ approach is usually undertaken, in which only exons that have been previously implicated are examined.

Date Last Reviewed: 05/2012

Genetic Testing for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Genetic testing for ARVC is covered for patients who meet the following criteria for Class I of the Heart Rhythm Society and the European Heart Rhythm Association recommendations:

• Mutation-specific genetic testing is covered for family members and appropriate relatives following the identification of the ACM/ARVC-causative mutation in an index case.

The following Class II indications will only be covered on a case by case basis:

Class IIa

• Comprehensive or targeted ACM/ARVC genetic testing for patients satisfying task force diagnostic criteria for ACM/ARVC.

Class IIb

• Genetic testing for patients with possible ACM/ARVC (1 major or 2 minor criteria) according to the 2010 task force criteria (European Heart Journal).

Arrhythmogenic right ventricular dysplasia/cardiomyopathy is a condition characterized by progressive fibro-fatty replacement of the myocardium that predisposes individuals to ventricular tachycardia and sudden death. The prevalence of ARVD/C is estimated to be 1 case per 10,000 populations. Familial occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been demonstrated. Recessive variants have been reported.  It is estimated that half of the individuals have a family history of ARVD/C and the remaining cases are new mutations.

Genetic testing has not been demonstrated to be necessary to establish the diagnosis of ARVD/C or determine its prognosis.  Twelve-lead ECG and echocardiography can be used to identify affected relatives.

Most affected individuals live a normal lifestyle. Management of individuals with ARVD/C is complicated by incomplete information on the natural history of the disease and the variability of disease expression even within families. High-risk individuals with signs and symptoms of ARVD/C are treated with anti-arrhythmic medications and those at highest risk who have been resuscitated or who are unresponsive to or intolerant of anti-arrhythmic therapy may be considered for an implantable cardioverter-defibrillator.

Date Last Reviewed:  05/2012

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 (81228, 81229, S3870) is considered experimental/investigational and not eligible for payment. There is insufficient evidence in the scientific research to support any positive effect on clinical outcomes. A participating, preferred, or network provider can bill the member for the denied test.

Date Last Reviewed: 04/2011

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 Bulletin U-6 for information on prenatal genetic testing.

See Medical Policy Bulletin L-33 for information on genetic testing for hereditary breast and/or ovarian cancer.

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.

Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Barahona-Dussault C, Benito B, Campuzano O, et al. Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Clin Genet. 2010 77:37-48.

Gollob MH, Blier L, Brugada R, et al.  Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol. 2011 Mar-Apr;27(2):232-45.

Hendrix A, Borleffs CJ, Vink A, et al. Cardiogenetic screening of first-degree relatives after sudden cardiac death in the young: a population-based approach. Europace. 2011 May;13(5):716-22.

Genetica Testing for Brugada

Svendsen JH, Geelen P. Screening for, and management of, possible arrhythmogenic syndromes (channelopathies/ion channel diseases). Europace. 2010 12:741-742.

Hofman N, Tan HL, Alders M, et al.  Active cascade screening in primary inherited arrhythmia syndromes: does it lead to prophylactic treatment? J AM Coll Cardiol. 2010 Jun 8;55(23):2570-6.

Gollob MH, Blier L, Brugada R, et al.  Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol. 2011 Mar-Apr;27(2):232-45.

Genetic Testing for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Gollob MH, Blier L, Brugada R, et al.  Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol. 2011 Mar-Apr;27(2):232-45.

Hofman N, Tan HL, Alders M, et al.  Active cascade screening in primary inherited arrhythmia syndromes: does it lead to prophylactic treatment? J AM Coll Cardiol. 2010 Jun 8;55(23):2570-6.

Genetic Testing for Mutations Associated with Malignant Melanoma Susceptibility

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

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.

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

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.

Genetic Testing for Diagnosis or Risk Assessment of Alzheimer's Disease

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

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

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

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

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

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

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

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

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

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

Hypertrophic Cardiomyopathy

Gollob MH, Blier L, Brugada R, et al.  Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol. 2011 Mar-Apr;27(2):232-45.

Ingles J, Zodgekar PR, Yeates L, et al. Guidelines for genetic testing of inherited cardiac disorders. Heart Lung Circ. 2011 Nov;20(11):681-7.

Hendrix A, Borleffs CJ, Vink A, et al. Cardiogenetic screening of first-degree relatives after sudden cardiac death in the young: a population-based approach. Europace. 2011 May;13(5):716-22.

Long-QT Syndrome

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

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

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

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.

McCormack J, MD, FACC. The role of genetic testing in paediatric syndromes of sudden death: state of the art and future considerations. Cardiology in the Young. 2009 19(2):54-65.

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.

Svendsen JH, Geelen P. Screening for, and management of, possible arrhythmogenic syndromes (channelopathies/ion channel diseases). Europace. 2010 12:741-742.

Hofman N, Tan HL, Alders M, et al.  Active cascade screening in primary inherited arrhythmia syndromes: does it lead to prophylactic treatment? J AM Coll Cardiol. 2010 Jun 8;55(23):2570-6.

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

Gollob MH, Blier L, Brugada R, et al.  Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol. 2011 Mar-Apr;27(2):232-45.

Ingles J, Zodgekar PR, Yeates L, et al. Guidelines for genetic testing of inherited cardiac disorders. Heart Lung Circ. 2011 Nov;20(11):681-7.

Hendrix A, Borleffs CJ, Vink A, et al. Cardiogenetic screening of first-degree relatives after sudden cardiac death in the young: a population-based approach. Europace. 2011 May;13(5):716-22.

Proto-Oncogene in Medullary Carcinoma of the Thyroid

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

Comparative Genomic Hybridization

Hochstenbach R, Binsbergen E, Engelen J, et al. Array analysis and karyotyping: Workflow consequences based on a retrospective study of 36,325 patients with idiopathic developmental delay in the Netherlands. European Journal of Medical Genetics. 2009;52:161-169.

Kleeman L, Bianchi D, Shaffer L. Use of array comparative genomic hybridization for prenatal diagnosis of fetuses with sonographic anomalies and normal metaphase karyotype. Prenatal Diagnosis. 2009;29:1213-1217.

Sagoo, G, Butterworth A, Sanderson S, et al. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genetic in Medicine. March 2009;11(3): 139-146.

Van den Veyver I, Patel A, Shaw C. Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300 cases. Prenat Diagn. 2009;29: 29-39.

Miller D, Adam M, Aradhya S, et al. Consensus Statement: Chromosomal Microarray is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies. Am J Human Genetics. May 14, 2010;86: 749-764/

Manning M, Hudgins L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. ACMG.Practice Guidelines. November 2010;12(11):742-745.

Autism Consortium Clinical Genetics/DNA Diagnostics Collaboration. Clinical Genetic Testing for Patients with Autism Spectrum Disorders. Pediatrics. 2010;125:e727-735.