Genetic Testing for Non-Cancerous Inheritable Diseases

Transcription

1 Genetic Testing for Non-Cancerous Inheritable Diseases Policy Number: Original Effective Date: MM /01/2010 Line(s) of Business: Current Effective Date: HMO; PPO; QUEST 05/01/2013 Section: Medicine Place(s) of Service: Outpatient I. Description A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to an inheritable disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing). Genetic tests are conducted for a number of purposes, including predicting disease risk, newborn screening, determining clinical management, identifying carriers, and establishing prenatal or clinical diagnoses or prognoses in individuals, families, or populations. For the purpose of this policy, first-degree relatives are defined as parents, full siblings, and offspring. Second-degree relatives are defined as grandparents, grandchildren, aunts, uncles, nephews, nieces, half-siblings and third-degree relatives are defined as great-grandparents, great-aunts, great-uncles, first cousins. This policy does not address oncology-related genetic testing or pre-implantation genetic diagnosis (PGD). II. Criteria/Guidelines A. Genetic testing for all the inheritable diseases listed below must meet the following factors (in addition to any specific criteria) in order to be covered: 1. There must be a reasonable expectation based on family history, pedigree analysis, risk factors, and/or symptomatology that a genetically inherited condition exists. 2. The genotypes to be detected by a genetic test must be shown by scientifically valid methods to be associated with the occurrence of the disease.

2 Genetic Testing for Non-Cancerous Inheritable Diseases 2 3. The analytical and clinical utility validity of the test must be established (e.g., test results will influence decisions concerning disease treatment or prevention). B. Genetic testing for the conditions listed below is covered (subject to Limitations/Exclusions and Administrative Guidelines) if after history, physical exam, pedigree analysis, and completion of conventional diagnostic studies, a definitive diagnosis remain uncertain. These include but are not limited to: Achrondroplasia (FGFR3) Amino acid metabolic disturbances Charcot-Marie Tooth disease (PMP-22) Classical lissencephaly Congenital hydrocephalus Cri-du-chat Cystic kidney disease (including polycystic kidney, autosomal dominant) Down's syndrome Dwarfism Fabry disease Factor XIII (F13) deficiency, congenital (Factor XIII beta globulin) Friedreich's ataxia (FRDA [frataxin]) Gonadal dysgenesis (Turner's, XO syndrome) Hereditary progressive muscular dystrophy (Duchene[dystrophin]-Becker's type(limb girdle muscular dystrophy [LGMD1, LGMD2])-Oculopharyngeal muscular dystrophy [OPMD])) Neurofibromatosis type 2 (Merlin) Osteogenesis imperfecta Phenylketonuria (PKU) Prader-Willi-Angelman syndrome (SNRPN, GABRA5, NIPA1, UBE3A, ANCR, GABRA) Peutz-jeghers Thanatophoric dysplasia (FGFR3) Tuberous sclerosis Turners syndrome Velo cardio facial syndrome(catch 22) Von Hippel-Lindau syndrome (VHL) Von Willebrand's disease The following genetic tests are covered (subject to Limitations/Exclusions and Administrative Guidelines) with precertification: C. Genetic testing for cystic fibrosis (CF) to determine carrier status in the following high-risk individuals: 1. Individuals with a positive family history of CF, limited to first- or second-degree relatives 2. Reproductive partner of an individual with CF or is a known carrier 3. Individuals with a first-degree relative identified as a CF carrier

3 Genetic Testing for Non-Cancerous Inheritable Diseases 3 D. Chromosomal microarray analysis for diagnosing a genetic abnormality in children with apparent nonsyndromic cognitive developmental delay /intellectual disability (DD/ID) or autism spectrum disorder (ASD) when ordered by a geneticist or pediatric neurologist when all of the following conditions are met: 1. Any indicated biochemical tests for metabolic disease have been performed, and results are non-diagnostic 2. The results from the genetic test have the potential to impact the clinical management of the patient 3. If DD/ID or ASD is diagnosed in conjunction with phenotypic features consistent with a specific syndrome for which confirmatory testing cannot be accomplished by other cytogenetic methods (i.e., routine or high-resolution karyotype analysis fluorescence in situ hybridization) E. Genetic testing for carrier status of spinal muscular atrophy (SMA) in high-risk individuals when ordered by a geneticist or pediatric neurologist meeting any of the following criteria: 1. Individuals with a positive family history of SMA, limited to first- or second-degree relatives 2. Reproductive partner of an individual with SMA or is a known SMA carrier 3. Individuals with a first-degree relative identified as a SMA carrier F. Genetic testing for fragile X syndrome for individuals in any of the following risk categories where the results of the test will affect clinical management or reproductive decisions: 1. Individuals with mental retardation (MR), DD, or ASD 2. Prenatal testing of fetuses of known carrier mothers 3. Individuals planning a pregnancy who have either of the following; a. A first- or second- degree relative with fragile X syndrome, or b. A first- or second- degree relative with MR, etiology unknown G. Genetic testing for carrier status of Tay-Sachs, Canavan disease, Familial Dysautomia and Gaucher s disease in individuals of Ashkenazi Jewish descent meeting the following high-risk indications: 1. A first-or second- degree relative with Tay-Sachs, Canavan disease, Familial Dysautomia, or Gaucher s disease 2. Reproductive partner of an individual with Tay-Sachs, Canavan disease, Familial Dysautomia, or Gaucher s disease or is a known Tay-Sachs, Canavan disease, Familial Dysautomia or Gaucher s disease carrier 3. A first-degree relative identified as a Tay-Sachs, Canavan disease, Familial Dysautomia or Gaucher s disease carrier H. Genetic testing for HFE-associated hereditary hemochromatosis (HHC) gene mutations: 1. For diagnostic testing when the individual with symptoms consistent with hemochromatosis and serum transferrin iron saturation is greater than or equal to 45%, but the diagnosis remain uncertain after completion of conventional testing 2. In individuals with a family history of hemochromatosis in a first degree relative I. Genetic testing for predisposition to hypertrophic cardiomyopathy (HCM) for individuals having one first-degree relative with established HCM.

4 Genetic Testing for Non-Cancerous Inheritable Diseases 4 J. Genetic testing for suspected congenital Long QT Syndrome (LQTS) for individuals who do not meet the clinical criteria for LQTS but have one of the following: 1. A first- or second- degree relative with a known LQTS mutation 2. A first- or second- degree relative diagnosed with LQTS by clinical means whose genetic status is unavailable 3. Signs and/or symptoms indicating a moderate to high pretest probability of LQTS, defined as a Schwartz score of 2-3. (See Table I in the Appendix) K. Genetic testing for Factor V Leiden and/or prothrombin G20210A mutation when any of the following criteria are met: 1. Age 50 or less, any venous thrombosis 2. Age 50 or less, in patients who develop acute arterial thrombosis in the absence of other risk factors for atherosclerotic arterial occlusive disease 3. Venous thrombosis in unusual sites (such as portal hepatic, mesenteric and cerebral veins) 4. Recurrent venous thrombosis 5. Venous thrombosis and a first-or second- degree relative with thrombotic disease 6. Venous thrombosis in pregnant women or women taking oral contraceptives 7. Women with recurrent pregnancy loss or unexplained severe preeclampsia, placental abruption, intrauterine fetal growth retardation or stillbirth 8. Myocardial infarction in female smokers under age 50 L. Genotypic or phenotypic analysis of the Thiopurine Methyltransferase (TPMT) gene is covered on a one time basis in individuals beginning therapy with azathioprine (AZA),mercaptopurine (6-MP) or thioguanine (6-TG) or in individuals on thiopurine therapy with abnormal complete blood count results that do not respond to dose reduction. M. Genetic testing for hemoglobinopathies (i.e., thalassemias and sickle cell disease) is covered when one of the following criteria is met: 1. For confirmation of a diagnosis in either of the following situations: a. For individuals with clinical features suggestive of a hemoglobinopathy when test results from conventional studies (e.g., Iron deficiency test and serum electrophoresis) are inconclusive and have failed a trial of iron therapy b. Infants who are diagnosed on newborn screening as having a hemoglobinopathy 2. For carrier testing in either of the following situations: a. When there is an affected first- or second- degree relative with thalassemia or sickle cell disease b. When the patient is the reproductive partner of a known carrier (disease-causing mutation of gene HBB, HBA1, or HBA2) and the couple has the capacity and intention to reproduce N. Because of the rapidly evolving field of genetic testing, this policy does not address every genetic test available. All other genetic tests not mentioned in this policy will be reviewed based on medical necessity and the policy criteria (II.A. 1-3).

5 Genetic Testing for Non-Cancerous Inheritable Diseases 5 III. Limitations/Exclusions A. The following genetic tests are not covered because they have not been shown to improve health outcomes: 1. Genetic testing to determine preterm labor 2. Genetic testing to determine warfarin sensitivity 3. Genetic testing for the diagnosis or risk assessment of Alzheimer's disease including but not limited to testing for, apolipoprotein E epsilon 4 allele, presenilin genes or amyloid precursor gene 4. Genetic testing for helicobacter pylori treatment B. Genetic testing is not covered in the following circumstances: 1. Family members of subscribers, who themselves are not subscribers or dependents 2. Members if the results of the genetic testing are for the benefit of relatives who are not subscribers or dependents C. Except as referenced in Criteria/Guidelines, genetic screening of individuals is not covered in the absence of associated signs, symptoms or complaints. General population screening for genetic disorders is not covered except where mandated by State and Federal law. D. Laboratories that conduct genetic testing must be CLIA certified. E. Genetic counseling is not a covered benefit. F. Genetic tests for a specific inherited disease will be covered once per lifetime unless new techniques that increase sensitivity are utilized. G. Home genetic testing is not a covered benefit. H. For a known deleterious mutation, HMSA will only cover a targeted single site analysis genetic test not a full analysis (i.e., testing for the mutation that has been identified in the family). IV. Administrative Guidelines A. For the genetic tests requiring precertification. Complete HMSA's Precertification Request and fax or mail the form as indicated with the following information: 1. Specify the condition for which the genetic test is being performed and if there are any known first- or second- degree relatives with the condition 2. Other types of biochemical testing apart from molecular genetic testing (enzyme activity assays, hemoglobin electrophoresis, blood chemistries, etc.), phenotypic findings and relevant clinical history and exam details 3. Specify how the results of the genetic test will impact the clinical management of the patient in terms of improving health outcomes B. Applicable codes requiring precertification for services rendered after January 1, 2013: CPT Description ASPA (aspartoacylase) (e.g. Canavan disease) gene analysis, common

6 Genetic Testing for Non-Cancerous Inheritable Diseases 6 variants (e.g. E285A, Y231X) CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; common variants CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis ;known familial variants CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; duplication/deletion variants CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; full gene sequence CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis;; intron 8 poly-t analysis Cytogenetic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants, (e.g., Bacterial Artificial Chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis) F2 (prothrombin, coagulation factor II) (e.g. hereditary hypercoagulability) gene analysis, 20210G>A variant F5 (coagulation factor V) (e.g. hereditary hypercoagulability) gene analysis, Leiden variant FMR1 (fragile X mental retardation 1) (e.g. fragile X mental retardation) gene analysis; evaluation to detect abnormal alleles FMR1 (fragile X mental retardation 1) (e.g. fragile X mental retardation) gene analysis; characterization of alleles GBA (glucosidase, beta, acid) (e.g., Gaucher disease) gene analysis, common variants (e.g., N370S, 84GG, l444p, IVS2+1G>A) HEXA (hexosaminidase A [alpha polypeptide]) (e.g., Tay-Sachs disease) gene analysis, common variants (e.g., 1278insTATC, G>C, G269S) HFE (hemochromatosis) gene analysis, common variants (e.g., C282Y, H63D) HBA1/HBA2 (alpha globin 1 and alpha globin 2) (e.g., alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis, for common deletions or variant (e.g., Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, and constant spring) Ikbkap (inhibitor of kappa light polypeptide gene enhancer in b-cells, kinase complex-associated protein) (eg, familial dysautonomia) gene analysis, common variants (eg, t>c, r696p) Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1,

7 Genetic Testing for Non-Cancerous Inheritable Diseases 7 KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1 and ANK2); full sequence analysis Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1 and ANK2); known familial sequence variant Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1 and ANK2); duplication/deletion variants MTHFR (5,10-methylenetetrahydrofolate reductase) (eg, hereditary hypercoagulability) gene analysis, common variants (eg, 677T, 1298C) ICD-9 codes Description Lipidoses Hereditary hemochomatosis Cystic Fibrosis (CTFR) Thalassemia(alpha globin/beta globin/hemoglobin E) Sickle-cell trait (hemoglobin S) Hb-SS disease without crisis Hb-SS disease with crisis Sickle-cell/Hb-C disease Other hemoglobinopathies (hemoglobin C) Autistic disorder, current or active state or residual state Mental retardation Cerebral lipidoses (Tay-Sachs disease) Spinal muscular atrophy (SBMA,SMN) Hypertrophic obstructive cardiomyopathy Long QT syndrome Regional enteritis Ulcerative colitis Habitual aborter; unspecified, with or without mention of antepartum condition (defined as two or more consecutive pregnancy losses)* Habitual aborter; antepartum condition or complication(defined as two or more consecutive pregnancy losses)*

8 Genetic Testing for Non-Cancerous Inheritable Diseases Fragile X syndrome Delayed milestone V12.51 Personal history of venous thrombosis and embolism V17.41 Family history of sudden cardiac death (SCD) V82.4 Maternal postnatal screening for chromosomal anomalies V83.81 Cystic fibrosis gene carrier * Definition from the American College of Obstetricians and Gynecologists: Practice Bulletin #24 C. Applicable codes for services rendered prior to January 1, 2013 requiring precertification: HCPCS S3845 S3846 S3850 S3865 S3866 S3870 Description Genetic testing for alpha-thalassemia Genetic testing for hemoglobin E beta-thalassemia Genetic testing for sickle cell anemia Comprehensive gene sequence analysis for hypertrophic cardiomyopathy Genetic analysis for a specific gene mutation for hypertrophic cardiomyopathy (HCM) in an individual with a known HCM mutation in the family Comparative genomic hybridization (CGH) microarray test for developmental delay/ autism spectrum disorder and/or mental retardation D. Codes for services rendered after January 1, 2013 that do not require precertification: DMD (dystrophin) (eg, Duchenne/Becker muscular dystrophy) deletion analysis, and duplication analysis, if performed BCKDHB (branched-chain keto acid dehydrogenase E1, beta polypeptide) (e.g. Maple syrup urine disease) gene analysis, common variants (e.g. R183P, G278S, E422X) MCOLN1 (mucolipin 1) (eg, mucolipidosis, type iv) gene analysis, common variants (eg, ivs3-2a>g, del6.4kb) PMP22 (peripheral myelin protein 22) (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; duplication/deletion analysis

9 Genetic Testing for Non-Cancerous Inheritable Diseases PMP22 (peripheral myelin protein 22) (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; full sequence analysis PMP22 (peripheral myelin protein 22) (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis ;known familial variant SMPD1(sphingomyelin phosphodiesterase 1, acid lysosomal) (e.g., Niemann- Pick disease, type A) gene analysis, common variants (e.g., R496L, L302P, fsp330) SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (e.g., Prader-Willi syndrome and/or Angelman syndrome), methylation analysis HCPCS S3842 S3853 Description Genetic testing for Von Hippel-Lindau disease Genetic testing for myotonic muscular dystrophy E. Codes for services rendered prior to January 1, 2013: HCPCS S3842 S3849 S3853 Description Genetic testing for Von Hippel-Lindau disease Genetic testing for Niemann-Pick disease Genetic testing for myotonic muscular dystrophy ICD-9 Description Neurofibromatosis, type 1 (neurofibromin) Neurofibromatosis, type 2 (Merlin) Dwarfism, not elsewhere classified [hypochondroplasia, thanatophoric dysplasia (FGFR3)] Phenylkentonuria (PKU) Other disturbances of aromatic amino-acid metabolism (includes albinism) Disturbances of branched-chain amino acid metabolism (includes maple syrup urine disease) Disturbances of suphur-bearing amino-acid metabolism (includes homocystinuria) Mucopolysaccharidosis (MPS-1)

10 Genetic Testing for Non-Cancerous Inheritable Diseases Congenital factor VIII disorder (hemophilia A/VWF) Congenital factor IX disorder([hemophilia B) Von Willebrand's disease Leukodystrophy Huntington's chorea (Huntington's disease) Friedreich's ataxia (frataxin) Peroneal muscular atrophy (Charcot-Marie-Tooth disease) Hereditary progressive muscular dystrophy( [Duchene (dystrophin)] [Becker's type] [limb girdle muscular dystrophy (LGMD1, LGMD2)] [oculopharyngeal muscular dystrophy (OPMD)]) Myotonic disorders (myotonic dystrophy {CMPK, ZNF-9}) Reduction deformities of brain (classical lissencephaly) Cystic kidney disease (including polycystic kidney, autosomal dominant) Chondrodystrophy (achondroplasia) Osteogenesis imperfecta Down's syndrome Autosomal deletion syndromes; cri-du-chat syndrome Velo-cardio-facial syndrome [22q11 deletion syndrome (CATCH-22)] Gonadal dysgenesis (ovarian dysgenesis, Turner's syndrome, XO syndrome) Klinefelter's syndrome Other hamartoses, not elsewhere classified (Von Hippel Lindau syndrome) Prader-Willi syndrome (GABRA, SNRPN) V13.69 Personal history of other congenital malformations V18.61 Family history of polycystic kidney disease V77.3 Special screening for PKU V77.7 Special screening for other inborn errors of metabolism V83.01 Asymptomatic hemophilia A carrier V83.02 Symptomatic hemophilia A carrier Note: Molecular diagnostic testing (codes , ) and cytogenetic studies (codes ) can be reported prior to January 1, 2013 when there is no specific genetic testing CPT/HCPCS code. A genetic testing code modifier specifying the probe type or the condition being

11 Genetic Testing for Non-Cancerous Inheritable Diseases 11 tested can be appended to the CPT code to provide complete and precise information regarding the genetic test being performed. See Table II in the Appendix for a list of modifiers applicable to this policy. ICD-10 codes are provided for your information. These will not become effective until 10/1/2014: ICD-10 Description E34.3 Short stature due to endocrine disorder E70.0 Classical phenylketonuria E70.21 Tyrosinemia E70.29 Other disorders of tyrosine metabolism E70.30 Albinism, unspecified E70.8 Other disorders of aromatic amino-acid metabolism E71.0 Maple-syrup-urine disease E Methylmalonic acidemia E71.19 Other disorders of branched-chain amino-acid metabolism E71.2 Disorder of branched-chain amino-acid metabolism, unspecified E70.29 Other disorders of tyrosine metabolism E72.10 Disorders of sulfur-bearing amino-acid metabolism, unspecified E72.11 Homocystinuria E72.12 Methylenetetrahydrofolate reductase deficiency E72.19 Other disorders of sulfur-bearing amino-acid metabolism E75.02 Tay-Sachs disease E75.21 Fabry (-Anderson) disease E75.22 Gaucher disease E Niemann-Pick disease, unspecified E76.01 Hurler's syndrome E76.02 Hurler-Scheie E76.03 Scheie's syndrome E76.1 Mucopolysaccharidosis, type II E Morquio A mucopolysaccharidoses E Morquio B mucopolysaccharidoses E Morquio mucopolysaccharidoses, unspecified E76.22 Sanfilippo mucopolysaccharidoses E76.29 Other mucopolysaccharidoses E76.3 Mucopolysaccharidosis, unspecified D56.0 Alpha thalassemia

12 Genetic Testing for Non-Cancerous Inheritable Diseases 12 D56.1 Beta thalassemia D57.00 Hb-SS disease with crisis, unspecified D57.01 Hb-SS disease with acute chest syndrome D57.02 Hb-SS disease with splenic sequestration D57.1 Sickle-cell disease without crisis D57.20 Sickle-cell/Hb-C disease without crisis D Sickle-cell/Hb-C disease with acute chest syndrome D Sickle-cell/Hb-C disease with splenic sequestration D Sickle-cell/Hb-C disease with crisis, unspecified D57.3 Sickle-cell trait D57.40 Sickle-cell thalassemia without crisis D66 D67 Hereditary factor VIII deficiency Hereditary factor IX deficiency D68.0 Von Willebrand's disease E75.23 Krabbe disease E75.25 Metachromatic leukodystrophy E75.29 Other sphingolipidosis E77.0 Defects in post-translational modification of lysosomal enzymes E77.1 Defects in glycoprotein degradation E Hereditary hemochromatosis E84.0 Cystic fibrosis with pulmonary manifestations E84.19 Cystic fibrosis with other intestinal manifestations E84.8 Cystic fibrosis with other manifestations F84.0 Autistic disorder F70-F79 Mental retardation, code range G10 Huntington's disease G11.1 Early-onset cerebellar ataxia G12.9 Spinal muscular atrophy, unspecified G60.0 Hereditary motor and sensory neuropathy G71.0 Muscular dystrophy G71.11 Myotonic muscular dystrophy G71.12 Myotonia congenita G71.13 Myotonic chondrodystrophy

13 Genetic Testing for Non-Cancerous Inheritable Diseases 13 G71.14 Drug induced myotonia G71.19 Other specified myotonic disorders I45.81 Long QT syndrome K50.00 Crohn's disease of small intestine without complications K51.80 Other ulcerative colitis without complications O26.20 Pregnancy care for patient with recurrent pregnancy loss, unspecified trimester O26.21 O26.23 Pregnancy care for patient with recurrent pregnancy loss (first, second, third trimester) Q04.1 Arhinencephaly Q04.2 Holoprosencephaly Q04.3 Other reduction deformities of brain Q55.4 Other congenital malformations of vas deferens, epididymis, seminal vesicles and prostate Q61.19 Other polycystic kidney, infantile type Q61.2 Polycystic kidney, adult type Q77.1 Thanatophoric short stature Q77.4 Achondroplasia Q77.8 Other osteochondrodysplasia with defects of growth of tubular bones and spine Q78.0 Osteogenesis imperfecta Q85.01 Neurofibromatosis, type 1 Q85.02 Neurofibromatosis, type 2 Q85.8 Other phakomatoses, not elsewhere classified Q87.1 Congenital malformation syndromes predominantly associated with short stature Q93.4 Deletion of short arm of chromosome Q93.81 Velo-cardio-facial syndrome Q96.9 Turner's syndrome, unspecified Q98.4 Klinefelter syndrome, unspecified Q99.2 Fragile X chromosome R62.0 Delayed milestone in childhood Z Encounter for screening for lipoid disorders Z Encounter for screening for other metabolic disorders Z13.4 Encounter for screening for certain developmental disorders in childhood Z13.89 Encounter for screening for other disorder Z14.01 Asymptomatic hemophilia A carrier Z14.02 Symptomatic hemophilia A carrier Z14.1 Cystic fibrosis carrier

14 Genetic Testing for Non-Cancerous Inheritable Diseases 14 Z15.89 Genetic susceptibility to other disease Z Encounter of female for testing for genetic disease carrier status for procreative management Z Encounter of male for testing for genetic disease carrier status for procreative management Z82.41 Family history of sudden cardiac death Z82.71 Family history of polycystic kidney Z82.79 Family history of other congenital malformations, deformations and chromosomal abnormalities Z84.81 Family history of carrier of genetic disease Z86.71 Personal history of venous thrombosis and embolism Z Personal history of other (corrected) congenital malformations V. Scientific Background This policy is based primarily on recommendations in the Final Report of the Task Force on Genetic Testing and the Secretary's Advisory Committee on Genetic Testing. The Task Force on Genetic Testing was an official government advisory group reporting to the National Advisory Council for Human Genome Research of the National Human Genome Research Institute, the National Institutes of Health. The Secretary's Advisory Committee on Genetic Testing (SACGT) was established to advise the Department of Health and Human Services on the medical, scientific, ethical, legal, and social issues raised by the development and use of genetic tests. Many genetic tests are imperfect predictors of either existing disease or disease susceptibility, particularly when used in the context of population screening, where individuals without family histories of disease, risk factors or symptoms are tested. For example, the probability exists that a disease may still occur, even when a negative test result is obtained. Conversely, a specific disease may not occur when there is a positive test result. While these concepts hold true for at-risk individuals as well, the probability of both these occurrences is greater in population screening, so test results are more difficult to interpret in a manner that will meaningfully impact health outcomes. With a few limited exceptions (e.g., PKU testing), general screening of populations for diseases that can be attributed to genetic mutations is not advocated in the published scientific literature. Analytical validity Analytical validity is an indicator of how well a test measures the property or characteristic it is intended to measure, and it is made up of three components Analytical sensitivity: the test is positive when the relevant gene mutation is present. Analytical specificity: the test is negative when the gene mutation is absent and reliability: the test obtains the same result each time. Clinical Validity Clinical validity in genetic testing is a measurement of the accuracy with which a test identifies or predicts a clinical condition and involves the following: 1. Clinical sensitivity: the probability that the test is positive if the individual being tested actually has the disease or a predisposition to the disease.

15 Genetic Testing for Non-Cancerous Inheritable Diseases Clinical specificity: the probability that the test is negative if the individual does not have the disease or a predisposition to the disease. 3. Positive predictive value: the probability that an individual with positive test results will get the disease. 4. Negative predictive value: the probability that an individual with negative test results will not get the disease. 5. Heterogeneity: different mutations within the same gene may cause the same disease and can result in different degrees of disease severity; a failure to detect all disease-related mutations reduces a test's clinical sensitivity. 6. Penetrance: the probability that the disease will appear when a disease-related genotype is present. Penetrance is incomplete when other genetic or environmental factors must be present for a disease to develop. The clinical utility of the test must be established. The development of genetic tests that can diagnose or predict disease occurrence has far outpaced the development of interventions to treat, ameliorate or prevent those same diseases. Clinical utility refers to the ability of genetic test results, either positive or negative, to provide information that is of value in the clinical setting. Specifically for positive test results, this could involve instituting treatments or surveillance measures, making decisions concerning future conception, or avoiding harmful treatments. Negative test results can have clinical utility in that unnecessary treatments or surveillance can be avoided. In the absence of such interventions, the benefits of testing are limited, and in fact, can cause psychological harm. Genetic testing of children to confirm current symptomatology or predict adult onset diseases is not considered medically necessary unless direct medical benefit will accrue to the child and in the case of adult onset disease, this benefit would be lost by waiting until the child has reached adulthood. It is generally accepted in the published literature that unless useful medical intervention can be offered to children as a result of testing, formal testing should wait until the child is old enough to understand the consequences of testing and request it for him or herself. Ethical concerns related to the testing of children include the breach of confidentiality that is required by revealing test results to parents, the lack of ability to counsel the child in a meaningful way regarding the risks and benefits of testing, the impact a positive test could have in terms of discrimination, and the potential psychological damage that could occur from distorting a family s perception of the child. VI. Important Reminder The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is intended to discourage or prohibit providing other medical advice or treatment deemed appropriate by the treating physician. Benefit determinations are subject to applicable member contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. This Medical Policy has been developed through consideration of the medical necessity criteria under Hawaii s Patients Bill of Rights and Responsibilities Act (Hawaii Revised Statutes 432E-1.4), generally

16 Genetic Testing for Non-Cancerous Inheritable Diseases 16 accepted standards of medical practice and review of medical literature and government approval status. HMSA has determined that services not covered under this Medical Policy will not be medically necessary under Hawaii law in most cases. If a treating physician disagrees with HMSA s determination as to medical necessity in a given case, the physician may request that HMSA consider the application of this Medical Policy to the case at issue. VII. References 1. Secretary's Advisory Committee on Genetic Testing. A public consultation on oversight of genetic tests. December 1, January 31, National Institute of Health. Verified 10/25/ U.S. Preventive Services Task Force. Screening for hemochromatosis: Recommendation statement. Ann Intern Med Aug 1;145(3): American College of Medical Genetic (ACMG) Practice Guidelines; Carrier screening for Spinal Muscular Atrophy. November ACMG Practice Guidelines; Carrier screening in individuals of Ashkenazi descent. November ACMG Practice Guidelines; Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. April ACMG Practice Guidelines; Fragile X Syndrome: Diagnostic and carrier testing. October ACMG Consensus Statement on Factor V Leiden Mutation testing. Reaffirmed 05/14/ BCBSA Medical Policy Reference Manual. Pharmacogenetic and Metabolite Markers for Patients Treated with Thiopurines # Last reviewed June ACMG Standards and Guidelines for Clinical Genetics Laboratories. Technical Standards and Guidelines: Venous Thromboembolism (Factor V Leiden and Prothrombin 20210G>A Testing): A Disease-Specific Supplement to the Standards and Guidelines for Clinical Genetics Laboratories BCBSA Medical Advisory Panel. Special Report: Evaluating evidence supporting a role for genetic markers assessing disease predisposition and prognosis, or predicting response to therapy. June 10, BCBSA Technology Evaluation Center Genetic testing for long QT syndrome. TEC Assessment 2007; volume 22 tab American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG). Preconception and Prenatal Carrier Screening for Cystic Fibrosis: Clinical and Laboratory Provider Guidelines. ACOG/ACMG Position Statement. Washington, DC: ACOG; Genetic testing for HFE gene mutations related to hereditary hemochromatosis. BCBSA Technology Evaluation Center. Chicago, IL: April 2002; 16(22) 14. Special Report: Molecular karyotyping by array comparative genomic hybridization (acgh) for the genetic evaluation of patients with developmental delay/mental retardation and autism spectrum disorder. BCBSA Medical Advisory Panel. December American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin #24. Testing guidelines for early recurrent pregnancy loss 16. BCBSA Medical Policy Reference Manual. Genetic Testing for Helicobacter pylori Treatment- Archived. # Reviewed July BCBSA Medical Policy Reference Manual. Genetic Testing for Hereditary Hemochromatosis. # Created April 2012

17 Genetic Testing for Non-Cancerous Inheritable Diseases BCBSA Medical Policy Reference Manual. Chromosomal Microarray (CMA) Analysis for the Genetic Evaluation of Patients with Developmental Delay/Intellectual Disability or Autism Spectrum Disorder. # Reviewed December BCBSA Tec Assessment. Genetic Testing for Predisposition to Inherited Hypertrophic Cardiomyopathy. Vol. 34, No.11. August National Institute of Health. Genetics Home Reference. Sickle cell disease. Reviewed February BCBSA Medical Policy Reference Manual. Genetic Testing for FMR1 Mutations (Including Fragile X Syndrome). # Created June, BCBSA Medical Policy Reference Manual. Genetic Testing for Predisposition to Inherited Hypertrophic Cardiomyopathy. # Created December Genetic Testing for Cystic Fibrosis. NIH Consensus Statement 1997 Apr 14-16;15(4): VIII. Appendix Table 1 LQTS Clinical Probability Score Card (i.e., Schwartz Score) Finding History Clinical history of syncope*without stress with stress Congenital deafness Family history of LQTS* Unexplained sudden death in a first-degree family < 30 yrs. old* ECG Corrected QT interval (QTc by Bazett s formula) 450 ms (in males) ms >480 ms Torsade de pointes** T-wave alternans >3 Leads with notched T waves Bradycardia (<second percentile for age) Points

18 Genetic Testing for Non-Cancerous Inheritable Diseases 18 A score <1 =low probability; 1 to <4 =intermediate probability; > 4=high probability. * Cannot count the same family member for both criteria ** Syncope and torsade de pointes are mutually exclusive Table II. Genetic code modifiers: This listing of two-character modifiers is categorized by mutation. Genetic testing code modifiers should be used in conjunction with CPT and HCPCS codes to provide diagnostic granularity of service to enable providers to submit complete and precise genetic testing information without altering test descriptors. Modifier Description 0C Neurofibromin (Neurofibromatosis, type 1) 0D Merlin (Neurofibromatosis, type 2) 0F 3A 3D 3E 3F 3G 3H VHL (Von Hippel Lindau disease) F5 commonly called Factor V (Leiden, others) (Hypercoagulable state) HBB, beta globin (Thalassemia, Sickle cell anemia, other hemoglobinopathies) HBA, commonly called alpha globin (Thalassemia) MTHFR (Elevated homocystinemia) F2, commonly called prothrombin (20210, others)(hypercoagulable state) Prothrombin (Factor II, 20210A)Hypercoagulable state F8, commonly called Factor VIII (Hemophilia A/VWF) 3I F9, commonly called Factor IX (Hemophilia B) 3K 5A 5B 5C 5D 5E 5H F13, commonly called Factor XIII (bleeding or hypercoagulable state) Beta globin ASPA, commonly called Aspartoacylase A (Canavan disease) FMR-1 (Fragile X, FRAXA, syndrome) FRDA commonly called Frataxin (Freidreich ataxia) HD commonly called Huntington (Huntington's disease) GABRA5, NIPA1, UBE3A, or ANCR GABRA (Prader Willi-Angelman syndrome) SNRPN (Prader Willi-Angelman syndrome) 5N PMP-22(Charcot-Marie-Tooth disease, type 1A)

19 Genetic Testing for Non-Cancerous Inheritable Diseases 19 6A DMD (Duchenne/Becker muscular dystrophy) 6B DMPK (Myotonic dystrophy, type 1) 6C ZNF-9 (Myotonic dystrophy, type 2) 6D 7B 7C 8A 8C 9A 9N 9O 9Q SMN1/SMN2 (Autosomal recessive spinal muscular atrophy) NPC1 or NPC2 (Nieman-Pick disease) GBA (Gaucher disease) CFRT (Cystic fibrosis) LQTS, KCN (Jervell and Lange-Nielsen syndromes, types 1, 2, 5, and 6) and SCN (Brugada syndrome, SIDS and type 3) TPMT, Patients on antimetabolite therapy FGFR2 (Crouzon, Jackson-Weiss, Apert, Saethre-Chotzen syndromes) FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, types I and II, Crouzon syndrome with acanthosis nigricans, Muencke syndromes) DGCR, commonly called CATCH-22 (DiGeorge and 22q11 deletion syndromes)