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Genetic Testing for Non-Cancerous Inheritable Diseases

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Genetic Testing for Non-Cancerous Inheritable Diseases Genetic Testing for Non-Cancerous Inheritable Diseases Policy Number: Original Effective Date: MM.02.009 03/01/2010 Line(s) of Business: Current Effective Date: HMO; PPO; QUEST 11/01/2013 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. 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). Genetic Testing for Non-Cancerous Inheritable Diseases 2 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 D. Chromosomal microarray analysis for diagnosing a genetic abnormality in children with apparent nonsyndromic cognitive developmental delay /intellectual disability (DD/ID) or autism spectrum Genetic Testing for Non-Cancerous Inheritable Diseases 3 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. 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
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